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PubMed2003

Mast cell infiltration and chemokine expression in progressive renal disease.

BACKGROUND: Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis. METHODS: Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressive, nonimmune-mediated renal injury. In addition, expression of the profibrotic cytokine, transforming growth factor-beta (TGF-beta) within mast cells and the effects of renoprotective therapy with angiotensin-converting enzyme (ACE) inhibition were also determined. RESULTS: Renal injury was accompanied by mast cell infiltration, in close proximity to areas of tubulointerstitial fibrosis. Mast cells displayed toluidine blue metachromasia and were immunopositive for TGF-beta1 as well as chymase and tryptase. The expression of several mast cell chemokines, including stem cell factor, interleukin-8 (IL-8), and also TGF-beta1, were increased in 5/6 nephrectomized kidneys. ACE inhibition with ramipril led to a reduction in renal injury in association with attenuation of mast cell infiltration and chemokine expression. CONCLUSION: Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA-salt rats.

Expression of the chemoattractant osteopontin (OPN) may contribute to macrophage infiltration in many types of tubulointerstitial kidney disease, but the role of OPN in chronic glomerulosclerosis is unknown. We hypothesized that glomerular OPN expression and macrophage infiltration occur in deoxycorticosterone acetate (DOCA)-salt glomerulosclerosis in rats. Uninephrectomized rats receiving DOCA pellets and 1% saline were compared with control rats. OPN mRNA was determined by Northern blot, and OPN protein was determined by Western blot. The localization of OPN was studied by in situ hybridization and double immunohistochemistry with glomerular cell markers. Macrophage infiltration was quantified by counting ED-1-positive cells, and semiquantitative glomerulosclerosis scores were obtained. In DOCA-salt rats, OPN mRNA in the kidney was increased 2-fold over control after 9 days and 3 weeks and 20-fold after 6 weeks. Tubulointerstitial OPN staining was apparent after 21 days of DOCA treatment. Glomerular OPN mRNA and protein was detected after 42 days in parietal and visceral epithelial cells, activated myofibroblasts, and occasionally mesangial cells. Progressive glomerular macrophage infiltration occurred during the development of DOCA hypertension, paralleling the degree of glomerulosclerosis. Glomeruli staining positive for osteopontin contained more macrophages (18.4 +/- 3.4 per cross-section) than osteopontin-negative glomeruli (3.6 +/- 0.5; P < 0.05). Glomerular OPN expression occurs in chronic hypertensive glomerulosclerosis and is associated with macrophage infiltration. The data suggest a role for OPN as a chemoattractant in hypertensive glomerulosclerosis.

Animals↗

PubMed2002

Portal lymphocytic infiltrate in alcoholic liver disease.

The aim of this study was to estimate the frequency of lymphocytic portal infiltrate in human alcoholic liver disease and to determine whether it was correlated with liver injury. This retrospective study included 200 consecutive patients referred between February 1996 and March 2001 to the Service Central d'Hépato-Gastroentérologie at Groupe Hospitalier Pitié-Salpêtrière Hospital, Paris, France. The inclusions criteria were as follows: (1) daily alcohol consumption greater than 40 g; (2) appropriate serological exclusion of B and C viral hepatitis; and (3) available liver biopsy specimen. Autoimmune hepatitis was excluded in all patients with the aid of a consensus scoring system. Forty percent of the patients had a predominantly lymphocytic portal infiltrate. On stepwise logistic regression of the predictive value of the 5 variables (gender, age, daily alcohol consumption, steatosis, and portal and septal fibrosis index), only 2 statistically independent predictors of predominant lymphocytic portal infiltrate were identified: portal and septal fibrosis index (P <.05) and age (P <.05). In conclusion, predominantly portal lymphocytic infiltrate occurs frequently in alcoholic liver disease, even in patients without serological markers of B and C viral hepatitis. Moreover, after adjustment for age, portal and septal fibrosis index remains significantly associated with the presence of a predominantly lymphocytic portal infiltrate. These results suggest that lymphocytes may play a role in the pathogenesis of alcohol-induced liver fibrosis.

Aged↗

PubMed2005

Suppression of macrophage infiltration inhibits activation of hepatic stellate cells and liver fibrogenesis in rats.

BACKGROUND & AIMS: Monocytes/macrophages infiltrate into injured livers. We tried to clarify their roles in inflammation and subsequent fibrogenesis by inhibiting their infiltration with a mutated form (7ND; 7 amino acids at the N-terminal were deleted) of monocyte chemoattractant protein 1, which may function as a dominant-negative mutant. METHODS: Rats were injected via the tail vein with an adenovirus expressing either human 7ND (Ad7ND), a truncated type II transforming growth factor beta receptor (AdTbeta-TR), which works as a dominant-negative receptor, bacterial beta-galactosidase (AdLacZ), or saline. Seven days later, the rats were treated with dimethylnitrosamine for 1-21 days. RESULTS: Within 24 hours after a single dimethylnitrosamine injection, macrophages were observed in livers. With a 3-day dimethylnitrosamine treatment, activated hepatic stellate cells were detectable in livers in AdLacZ-, AdTbeta-TR-, and saline-injected rats. In contrast, in the Ad7ND-treated rats, infiltration of macrophages was markedly reduced, and activated hepatic stellate cells were not detectable. After a 3-week dimethylnitrosamine treatment, fibrogenesis was almost completely inhibited, and activated hepatic stellate cells were hardly seen in livers in both Ad7ND- and AdTbeta-TR-treated rats. CONCLUSIONS: Our results show that blockade of macrophage infiltration inhibits activation of hepatic stellate cells and leads to suppression of liver fibrogenesis. The presence of activated hepatic stellate cells in the initial phase after injury and its absence at a later phase in the AdTbeta-TR-treated livers indicate that transforming growth factor beta is not an activating factor for hepatic stellate cells, and this suggests that transforming growth factor beta is required for the survival of activated hepatic stellate cells. Our study suggests that infiltrated macrophages may themselves produce an activating factor for hepatic stellate cells.

Animals↗

PubMedDate not supplied

Assessment of wound infiltration with bupivacaine in women undergoing day-case gynecological laparoscopy.

BACKGROUND AND OBJECTIVES: The effectiveness of local anesthetic wound infiltration for treatment of postoperative pain appears to be variable and partly dependent on the surgical procedure. Although evidence was lacking, it was common practice at our institution to infiltrate the trocar wound of patients undergoing day-case laparoscopic procedures with long acting local anesthetic agents. The aim of this study was to investigate the analgesic efficacy, and the influence of the timing, of local anesthetic infiltration into surgical wounds for day-case diagnostic gynecological laparoscopy. METHODS: A double-blind, randomized trial was conducted on 100 women having general anesthesia for day-case gynecological laparoscopy. Ninety-two patients who had been randomized to 1 of 4 groups for trocar wound infiltration with 30 mL of 0.25% bupivacaine or saline either before or after surgery completed the study. Incisional pain, pain on pressing the umbilicus, severity of nausea, and patient satisfaction with anesthetic technique were all assessed postoperatively until discharge and on the following day through a telephone interview. A P value of <.05 was considered significant. RESULTS: There was no difference between groups in the mean pain scores or analgesic requirements for incisional pain, pain on pressing firmly on the umbilicus, or for patient satisfaction. There was a trend for those patients who had received bupivacaine to use less postoperative morphine (P =.079). CONCLUSIONS: Wound infiltration with local anaesthetic did not significantly reduce pain or opioid requirement after gynecological laparoscopy.

Adult↗

PubMed1978

[Ultrasonic diagnosis in infiltrative gastrointestinal diseases (author's transl)].

The cockade phenomenon in the ultrasound picture is a sign of an infiltration of the gastrointestinal wall caused by tumour or inflammation. In 27 out of 40 patients with known infiltrations of the wall the cockade phenomenon could be demonstrated. In 16 out of 21 patients in whom this ultrasound phenomenon had primarily led to a suspected wall infiltration further diagnostic investigations proved organic wall thickening. Even if the cockade phenomenon is thus neither a specific nor a sensitive sign of gastrointestinal wall infiltrations the observation of this phenomenon is particularly important in patients in whom wall infiltrations of the gastrointestinal tract are not suspected.

Colonic Neoplasms↗

PubMed2005

Value of endorectal ultrasonography for diagnosing rectovaginal septal endometriosis infiltrating the rectum.

BACKGROUND AND STUDY AIMS: Rectovaginal septal endometriosis (RVSE) can pose serious therapeutic problems when there is infiltration of the rectal septum (which occurs in approximately half of the cases). The aim of this study was to assess the value of endoscopic ultrasonography in diagnosing rectal wall involvement by pelvic endometriosis. PATIENTS AND METHODS: A prospective study was carried out from May 1998 to March 2003 at a single hospital center. The 30 patients included in the study presented with suspected RVSE and underwent systematic anorectal endoscopic ultrasonographic exploration prior to the surgical intervention. The endoscopic ultrasonography was carried out under general anesthesia with a 7.5-MHz miniprobe equipped with a distal balloon. RESULTS: The anorectal endoscopic ultrasonographic examination (EUS) showed the presence of endometriosis in the rectovaginal septum in 26 patients (88 %), in the uterosacral ligaments in 10 patients (33 %), and in the ovaries in two patients (6 %). At EUS, the nodules were infiltrating the rectal wall in 17 patients (56 %). The surgical exploration demonstrated endometriosis in the rectovaginal septum in 26 cases, the uterosacral ligaments in 22 cases, and the ovaries in 16 cases. The rectal wall was completely infiltrated in 12 cases and only partly in four cases, and intestinal tract resection was required in 10 cases. The sensitivity, specificity, and positive and negative predictive value of anorectal endoscopic ultrasonography as a means of diagnosing endometriosis of the rectovaginal septum and infiltration of the rectal wall were found to be 96 %, 100 %, 100 % and 83 %, and 92 %, 66 %, 64 % and 92 %, respectively; and the diagnostic accuracy was at 96 % and 80 %, respectively. The sensitivity for detecting nodules in the uterosacral ligaments or in the ovaries was 42 % and 14 %, respectively, leading to diagnostic accuracy rates of 56 % and 53 %. CONCLUSIONS: In terms of its sensitivity and its negative predictive value, anorectal endoscopic ultrasonography is a very effective means of detecting endometriosis of the rectovaginal septum and assessing possible infiltration of the rectal wall. However, this method is not as accurate for nodules located far from the EUS probe, as is the case with the uterosacral ligaments and ovaries.

Adult↗

PubMed1998

[Magnetic resonance tomography in plasmacytoma: ranking of various sequences in diffuse and focal infiltration patterns].

PURPOSE: The aim of this study was to compare various pulse-sequences employing the spine array coil while considering the different infiltration patterns in multiple myeloma, in order to develop a fast and cost effective screening method. MATERIALS AND METHODS: In a prospective study, 50 patients with histologically proven multiple myeloma were examined with the following standardised sequences: T1-weighted SE, T2-weighted FSE, opposed phase GRE, FSE STIR, T1-weighted SE post gadopentate dimeglumine without and with fat saturation. The images were evaluated in a ROC analysis by three radiologists in consensus with a 5-grade scale separatively for diffuse and focal involvement. The gold standard was bone marrow histology in cases of diffuse infiltration and the combination of all sequences with the staging system according to Durie and Salmon. RESULTS: For focal bone marrow involvement the area under curve was greatest for FSE STIR sequences, in cases of diffuse infiltration the area under curve was superior for unenhanced T1-w SE-Sequenz images. The sensitivity can be increased by contrast material application and signal intensity measurements. A combined focal and diffuse infiltration and a "salt and pepper" pattern can be diagnosed with the combination of T1-w SE-Sequenz and FSE STIR sequences. CONCLUSION: With T1-weighted SE-Sequenz sequences pre- and post-contrast and FSE STIR all therapeutical relevant infiltration patterns of plasmocytoma can be identified and bone marrow screening of the spine can be carried out with an acquisition time of 5.58 minutes.

Adult↗

PubMed1997

[31P-MR spectroscopy of the human liver--the spectral indications of lymphoma infiltration].

PURPOSE: To evaluate whether phosphorus magnetic resonance spectroscopy (31P-MRS) enables a non-invasive detection of liver involvement in systemic diseases like Hodgkin's lymphoma. MATERIALS AND METHODS: Using a clinical 1.5 Tesla whole-body MR system image-guided localised phosphorus MR spectra from the anatomically defined volumes of interests were measured. A combination of surface coil, adiabatic excitation pulse and modified image-selected in vivo spectroscopy (ISIS)-sequence was applied. The spectroscopy data were evaluated quantitatively with a time-domain fit programme using non-linear optimisation algorithms to quantify peak areas. After establishment of the examination protocol, 22 healthy volunteers and 13 patients with suspected lymphoma infiltration of the liver were examined. RESULTS: Liver spectra of patients suffering from lymphoma infiltration differed significantly from spectra of persons with normal liver: 1. The peak area ratio of phosphomonoesters (PME) to beta-NTP was elevated in all patients with histologically confirmed liver lymphoma. 2. Patients suffering from Hodgkin's disease with specific or unspecific liver infiltration (n = 7) could be differentiated from patients without liver involvement. In case of infiltrated liver, the peak area ratio PME to beta-NTP was increased, and the pH value was shifted to lower values. Unambiguous differentiation between non-specific (n = 3) and specific (n = 4) infiltration of the liver was not possible. 3. In patients after cytostatic treatment (n = 3), an increase of the peak area ratio of inorganic phosphate to beta-NTP was observed. CONCLUSIONS: Our preliminary results indicate that 31P-MRS can yield pointers to liver involvement in patients with systemic diseases such as Hodgkin's disease, which may be hardly detected by imaging methods.

Adolescent↗

PubMed1989

[Detection of muscle, vein and artery infiltrations of cervical lymphatic metastases].

In a prospective study, 15 patients with squamous cell carcinomas of head and neck and clinical fixed cervical lymph node metastases were examined to determine the value of computed tomography, magnetic resonance imaging and high resolution real time ultrasonography in preoperative recognition of muscle and vessel infiltration. The preoperative findings were compared with the microscopic results of neck specimens and the operative reports. For each diagnostic method sensitivity, specificity, and effectivity were calculated. Ultrasonography, magnetic resonance imaging and computed tomography can assess muscle infiltrations as well. Metastatic infiltrations of carotid arteries are best recognised by ultrasonography and magnetic resonance imaging. Both methods are more valuable than computed tomography. All methods are unsuccessful in detecting infiltrations of the jugular vein. In conclusion, metastatic infiltrations of surrounding tissue, as described by imaging methods, are rarely confirmed by histological results.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

[Ultrasound image of the lumbar spine and the lumbosacral transition. Ultrasound anatomy and possibilities for ultrasonically-controlled facet joint infiltration].

QUESTION: Is sonography helpful in facet joint infiltration of the lumbar spine? METHOD: The sonoanatomy of the lumbar spine and the of lumbosacral junction was examined and described in a skeleton and in 10 volunteers. One representative cross section and 3 longitudinal sections were defined. According to these results (no neurological symptoms) the possibilities of ultrasound guided infiltration of the facet joints was examined in 78 patients (36 female, 42 male, average age 55 y., 38-78 y.) with chronic low back pain and increase of pain by hyperextension. 5 ml Carbostesin partially in combination with steroids were applied to each joint. In all cases the tip of the syringe could be placed on the joint. RESULTS: There were no complications, especially no infection or neurological symptoms. Application of local anaesthetics into the spinal canal could be excluded in all cases. The sonoanatomy of the lumbar spine and of the lumbosacral junction can be reproduced. Sonography allows an accurate infiltration of the facet joints of the lumbar spine. Applications into the spinal canal can be avoided. CONCLUSIONS: This method is a secure and economic (extra time 2-4 min.) alternative to clinically guided infiltration. Flouroscopy guided infiltration is needed only in anatomical variations or if strictly intraarticular application is necessary.

Adult↗

PubMed1994

[Painless infiltration anesthesia in eyelid surgery. An intraindividual randomized prospective study].

BACKGROUND: Local anesthetic infiltration before lid surgery causes pain of varying degrees. To reduce the patient discomfort we have tested the effect of an initial injection of deluted anesthetic prior to the infiltration anesthesia. PATIENTS AND METHODS: During August 1993 and April 1994 thirteen patients, 21 to 81 years of age had bilateral lid surgery (4 female; 9 male). Two injection techniques were studied in disease patients intraindividually. Part of the local anesthetic was deluted 1:10 with saline and initially injected on one side only. Three minutes later infiltration with 2-5 ml of full-strength 2% mepivacaine with adrenaline 1:200,000 was performed on both sides. Obvious signs of pain were documented and patients were questioned about their discomfort (score 0-3). RESULTS: Five patients were operated for bilateral ectropium (lateral canthal sling procedure 4, Lazy-T 1), seven patients for dermatochalasis and one patient for brow ptosis. All thirteen patients ranked the technique with the initial injection of deluted local anesthetic significantly less painful. 9 of 13 patients had painless local anesthetic infiltration. Only 4 patients reported minor discomfort during injection of the diluted anesthetic. Onset time and duration of anesthesia was identical in both groups. CONCLUSION: The initial injection of a 1:10 diluted local anesthetic allows a significant reduction of pain during infiltration anesthesia before lidsurgical procedures. While pH buffering with bicarbonate may cause permanent skin pigmentation, dilution with physiological saline is an effective and inexpensive alternative. With this technique even in children local anesthesia becomes possible.

Adult↗

PubMed1988

[Prognostic significance of lymphocytic infiltration in malignant melanoma of the choroid].

Lymphocytic infiltration of melanomas represents an immunological response of the organism to the tumor. In order to establish the prognostic significance of this parameter, 369 cases of malignant choroidal melanoma were investigated in the study reported here with respect to the degree of infiltration. The relationship to survival time and other histopathological parameters was examined by means of the mortality tabulation method. The 84.5% five-year survival rate among patients with melanomas exhibiting intense infiltration was significantly higher than the 70.9% rate among patients with tumors showing little infiltration. This study statistically confirms current conjecture that the degree of lymphocytic infiltration, already proven to be prognostically significant in cutaneous melanoma, is also prognostically significant in choroidal melanoma. No correlations to other histopathological parameters could be demonstrated.

Choroid↗

PubMed2000

Cardiovascular responses to epinephrine-containing local anesthetics for dental use: a comparison of hemodynamic responses to infiltration anesthesia and ergometer-stress testing.

OBJECTIVE: Cardiovascular effects of infiltration anesthesia have been documented in numerous studies. However, few studies have been carried out to compare the effects of infiltration anesthesia with the effects of exercise-stress testing. The purpose of this study was to examine this issue. STUDY DESIGN: Eight young and 13 older subjects were given infusions of epinephrine to produce cardiovascular responses comparable with those found in subjects undergoing infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E). Cardiovascular responses to this drug treatment were evaluated with echocardiography and compared with those produced by ergometer exercise. RESULTS: The hemodynamic effects of L-E infiltration anesthesia were less than those produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15 W in the older subjects. The workload of this ergometer-stress testing was about 4 metabolic equivalents (METS), which is approximately equivalent to the workload of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or pushing a power mower), painting, or doing light carpentry. CONCLUSION: With the exception of some specific pathologic conditions, such as serious arrhythmia, infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the patients who have exercise capacity of more than 4 METS.

Adult↗

PubMed2001

Anesthetic efficacy of ropivacaine in maxillary anterior infiltration.

OBJECTIVE: The purpose of this prospective, randomized double-blind study was to evaluate and compare the anesthetic efficacy of 0.5% ropivacaine with 1:200,000 epinephrine, of 0.5% ropivacaine, and of 0.5% bupivacaine with 1:200,000 epinephrine in maxillary lateral incisor infiltrations. STUDY DESIGN: Forty subjects randomly received, in a double-blind manner, 3 infiltrations at 3 separate appointments, in a repeated-measures design. The injections consisted of an infiltration of 1.8 mL of 0.5% ropivacaine plain, an infiltration of 1.8 mL of 0.5% ropivacaine with 1:200,000 epinephrine, and an infiltration of 1.8 mL of 0.5% bupivacaine with 1:200,000 epinephrine (control solution). The maxillary lateral incisor pulpal anesthesia was evaluated with an electric pulp tester at 2-minute cycles for 90 minutes after injection. No response from the subject to the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80 readings were obtained. The duration of pulpal anesthesia was recorded as the last 80 reading. RESULTS: One hundred percent of the subjects had lip numbness with all solutions. The anesthetic success rates for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine were 68%, 75%, and 80%, respectively. There were no significant differences (P >.05) among the solutions. The duration of pulpal anesthesia (80 readings) for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine was 13 minutes, 33 minutes, and 33 minutes, respectively. Ropivacaine plain had a significantly shorter duration of pulpal anesthesia than ropivacaine with epinephrine. CONCLUSIONS: We concluded that 0.5% ropivacaine with 1:200,000 epinephrine was equivalent to 0.5% bupivacaine with 1:200,000 epinephrine in pharmacologic action. The duration of pulpal anesthesia was less for ropivacaine without epinephrine. Ropivacaine with epinephrine has the potential to replace bupivacaine with epinephrine in clinical dental practice because of the decreased potential for cardiac and central nervous system toxicity.

Adult↗

PubMed2003

Genetic deletion of chemokine receptor CXCR3 or antibody blockade of its ligand IP-10 modulates posttransplantation graft-site lymphocytic infiltrates and prolongs functional graft survival in pancreatic islet allograft recipients.

BACKGROUND: Interaction of chemokine receptor CXCR3 with its ligand IP-10 mediates effector cell trafficking to sites of allograft rejection in murine models of whole organ allotransplantation. We hypothesized that blocking the CXCR3/IP-10 interaction would impair posttransplantation leukocyte trafficking to and delay rejection of pancreatic islet allografts. METHODS: A/J strain murine islets were implanted to the kidney capsule of H-2 disparate, streptozotocin-induced diabetic wild type (WT), CXCR3 deficient (CXCR3(-/-)) or IP-10 antibody-treated WT (alphaIP-10) C57BL/6 recipients. Representative grafts from each group were harvested at day 7. Ribonuclease protection assay was used to determine gene expression for cell markers F4/80 (macrophages), CD8 (type I T cells), CD4 (type II T cells), and CD 19 (natural killer cells), and for chemokines IP-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES. Immunohistochemistry was used to confirm ribonuclease protection assay infiltrate data. Graft-site chemokine gene expression and cellular infiltrate were correlated with time to functional graft rejection. RESULTS: Untreated WT recipients demonstrated heavy graft-site cell infiltrates and increased graft-site gene expression for cell markers F4/80, CD8, CD4, and CD19, and for chemokines RANTES, IP-10, and MIP-1beta at day 7. In comparison with untreated WT, alphaIP-10-treated WT and CXCR3(-/-) recipients demonstrated the same degree of chemokine gene expression but less lymphocytic infiltrate. The mean length of allograft survival was 12.7 +/- 3.1 days in untreated WT versus 20.2 +/- 2.7 days (P <.05) for CXCR3(-/-)- and 19.7 +/- 2.3 days (P <.05) for alphaIP-10-treated WT recipients. CONCLUSIONS: CXCR3 gene deletion or alphaIP-10 antibody therapy modulates posttransplantation lymphocytic graft infiltration and statistically prolongs graft survival in murine islet allograft recipients.

Animals↗

PubMed2003

Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction.

Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.

Animals↗

PubMed1998

The role of platelet-activating factor in cell infiltration in endotoxin-induced uveitis in guinea pigs.

PURPOSE: We investigated the role of platelet-activating factor (PAF) in cell infiltration in endotoxin-induced uveitis (EIU) in guinea pigs. METHODS: To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. PAF and prostaglandin E2 (PGE2) production after LPS injection were also examined. RESULTS: Intracameral injection of LPS induced cell infiltration into the anterior chamber, and platelet-activating factor (PAF) was detected in the aqueous humor. In addition, topical apafant (PAF antagonist) partially inhibited cell infiltration. Intracameral injection of PAF scarcely induced cell infiltration but the reaction with EIU was accelerated by intracameral injection of a small amount of PAF. CONCLUSIONS: These results suggest that PAF has weak direct activity on cell infiltration in intraocular inflammation but enhances intraocular inflammation.

Animals↗