PubMed Health⌕ Search

Biomedical subjects

L Lindbom

Publications and source records attributed to L Lindbom.

At least 37 records · Page 2Linked to original sources
PubMed1997

In vivo rolling and endothelial selectin binding of mononuclear leukocytes is distinct from that of polymorphonuclear cells.

In inflammation, rolling of leukocytes along the microvascular endothelium is a precondition for subsequent integrin-mediated firm adhesion and extravasation. Rolling characteristics of polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL) in small venules (15-25 microns) of the rat mesentery were studied by intravital fluorescence microscopy under basal conditions and after intravenous treatment with an anti-rat neutrophil serum (ANS). The baseline rolling fraction of the venular total leukocyte flux was 36 +/- 15% (mean +/- SD). The PMNL fraction of the systemic leukocyte count was 27 +/- 9%. Treatment with ANS resulted in total depletion of circulating PMNL and reduced the leukocyte rolling fraction to 12 +/- 5%, in this situation represented only by MNL. In rats treated intraperitoneally with interleukin (IL)-1 beta for 4 h, the leukocyte rolling fraction was 53 +/- 13% and was reduced to 33 +/- 11% after ANS treatment. These data indicated that most, if not all, circulating PMNL rolled along the venular endothelial lining in the rat mesentery prepared for intravital microscopy, whereas MNL rolling was minor (approximately 10%) under the same basal condition. In cytokine-activated tissue, on the other hand, the number of rolling MNL was greatly increased. While PMNL rolling is known to be entirely selectin dependent, the increased MNL rolling after IL-1 stimulation was likely mediated by alpha 4 integrins, inasmuch as the rolling fraction of isolated peripheral blood lymphocytes injected into the microcirculation of the cytokine-stimulated mesentery was reduced from 31 +/- 14% to 6 +/- 2% by pretreatment of the cells with a monoclonal antibody against the rat integrin alpha 4 chain. In accordance with the in vivo rolling characteristics of the two cell populations, binding of soluble P- or E-selectin (selectin/IgG chimeras) was less intense for blood lymphocytes than for granulocytes, as determined by flow cytometric analyses of rat and human leukocytes. Taken together, our findings in vivo indicate that the adhesive interactions responsible for rolling of PMNL and MNL, respectively, are distinct in terms of receptor occupancy, and may help explain the temporal selectivity in recruitment of different leukocyte subpopulations in inflammatory or immune reactions.

Animals↗
PubMed1997

Tumor cell arrest in the microcirculation: lack of evidence for a leukocyte-like rolling adhesive interaction with vascular endothelium in vivo.

Hematogenous spread of tumor cells and metastasis formation in secondary organs are insidious aspects of cancer. In the present intravital microscopic study in the rabbit mesentery, we examined the in vivo flow behavior of six human tumor cell lines of different histological origin. The tumor cells and human neutrophils were injected locally into a side branch of the superior mesenteric artery upstream of the observed microvascular area in the mesentery. None of the tumor cells behaved similar to the leukocytes of which a substantial fraction rolled along the endothelium of small venules. Thus, the tumor cells passed the same venular segments without interacting with the endothelial lining. Yet, three of the tumor cell lines (HT-29, DLD-1, and HCT-8) were strongly positive for the oligosaccharides Lewis(x), sialyl-Lewis(x), and sialyl-Lewis(a) which are recognized by the endothelial selectins that mediate leukocyte rolling. On the other hand, some tumor cells were trapped in the smallest vessels and remained so throughout the experimental period, apparently due to a discrepancy in size between tumor cells and microvessel lumen. Taken together, our in vivo findings suggest that initial microvascular arrest of metastasizing tumor cells is dependent primarily on mechanical factors rather than on receptor-mediated leukocyte-like adhesive interactions.

Animals↗
PubMed1997

Inhibitory effect of locally administered heparin on leukocyte rolling and chemoattractant-induced firm adhesion in rat mesenteric venules in vivo.

1. Anti-inflammatory actions of heparin and related glycosaminoglycans have been described in the literature. Here, we used intravital microscopy of the rat mesentery microcirculation to examine effects of locally administered heparin on leukocyte rolling and chemoattractant-induced firm adhesion. 2. It was found that topical application of heparin reduced N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced leukocyte adhesion. Notably, the inhibitory action of heparin was not dose-dependent, but rather a biphasic dose-response was found, i.e. low (2 and 20 iu ml(-1)) and high (1000 iu ml(-1)) concentrations of heparin significantly reduced adhesion, whereas an intermediate dose (200 iu ml(-1)) was less effective. 3. Heparin, 2 and 20 iu ml(-1), decreased rolling leukocyte flux, while having no effect on blood flow or total leukocyte flux. By contrast, heparin, 200 and 1000 iu ml(-1), increased total leukocyte flux in parallel with a rise in volume blood flow resulting in recovery of the rolling leukocyte flux at these doses. Thus, the biphasic inhibitory action of heparin on fMLP-induced firm adhesion could in part be attributed to changes in leukocyte delivery (i.e. blood flow) and rolling leukocyte flux induced by heparin. 4. When compensating for the influence of different rolling levels on fMLP-evoked adhesion, a dose-related inhibitory effect of heparin on the firm adhesive response per se was revealed. Similar results were obtained in a static adhesion assay in vitro where heparin 200 and 1000 iu ml(-1) (but not 2 and 20 iu ml(-1)) significantly inhibited fMLP-induced leukocyte adhesion in the absence of any modulatory influence on changes in rolling. 5. Our data show that locally administered heparin inhibits leukocyte rolling as well as chemoattractant-induced firm adhesion in vivo which thus may contribute to the postulated anti-inflammatory activity of this compound. However, because of interference with several microvascular functions, strict dose-dependent responses to heparin treatment were not found, which illustrates the complex interplay between local blood flow, leukocyte rolling and chemoattractant-induced adhesion as determinants of leukocyte recruitment to tissues in inflammation.

Administration, Topical↗
PubMed1997

Impaired leucocyte rolling, adhesion and transendothelial migration following cuprophane haemodialysis.

In this study, we investigated how different steps in the extravasation process of leucocytes, i.e. rolling, adhesion and transendothelial migration, are affected by haemodialysis with cuprophane membranes. Human leucocytes obtained from whole blood prior to clinical haemodialysis and from the afferent blood line (post-dialyser) 15 min after the initiation of dialysis were injected into the mesenteric microcirculation of urethane anaesthetized rabbits and analysed for their ability to roll in the microvessels by use of intravital fluorescence microscopy. Moreover, neutrophils from the two leucocyte populations were compared with respect to chemoattractant-induced adhesion and transmigration across confluent monolayers of bovine aortic endothelial cells. Our results show that, as compared with pre-dialysis leucocytes, 15 min of cuprophane haemodialysis impaired leucocyte rolling by 78 +/- 7%, reduced N-formyl-methionyl-leucyl-phenylalanin (fMLP)-induced adhesion by 34 +/- 9%, and abolished transendothelial migration. These findings demonstrate that intradialytical activation of leucocytes during cuprophane haemodialysis severely affects leucocyte functions that are critical in the extravasation process of these cells at inflammatory tissue sites, and thus may help explain the increased susceptibility to infections observed in patients on chronic haemodialysis.

Animals↗
PubMed1997

Cytokine-induced leukocyte rolling in mouse cremaster muscle arterioles in P-selectin dependent.

Leukocyte rolling and adhesion are generally observed in venules but rarely observed in arterioles. With the use of intravital microscopy, we found that a 4-h treatment with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) dose dependently induced leukocyte rolling and adhesion in arterioles of the mouse cremaster muscle. The rolling response lasted more than 24 h and was completely inhibited by treatment with the sulfated polysaccharide fucoidin. Moreover, we found that costimulation with IL-1beta and TNF-alpha for 4 h synergistically increased arteriolar leukocyte rolling, i.e., threshold doses of IL-1beta and TNF-alpha together caused a more than 10-fold increase of rolling in arterioles compared with the sum of the individual responses. This rolling interaction was abolished by treatment with a monoclonal antibody directed against P-selectin (RB40.34), but it apparently was unaffected by a monoclonal antibody against L-selectin (MEL-14). Taken together, our functional data show that IL-1beta and TNF-alpha separately induce and synergistically increase P-selectin-dependent leukocyte rolling and firm adhesion in mouse cremaster arterioles.

Animals↗
PubMed1997

Microvascular actions of histamine: synergism with leukotriene B4 and role in allergic leucocyte recruitment.

BACKGROUND: Previous studies have shown that antihistamines provide little or no protection against the recruitment of leucocytes in allergic inflammation. OBJECTIVE: We wanted to examine if threshold doses of histamine can potentiate chemoattractant-induced leukocyte adhesion and if complete inhibition of histamine-induced microvascular effects is necessary to reduce allergic leucocyte recruitment. METHODS: The role of histamine in allergic leucocyte recruitment was examined by use of intravital microscopy of the hamster cheek pouch microcirculation. RESULTS: We found that topical administration of histamine caused a concentration-dependent increase in microvascular permeability in the cheek pouch; i.e. 0.3 microM histamine caused no detectable plasma leakage, while 1 microM and 10 microM histamine resulted in 29 +/- 9.3 and 356 +/- 47 leakage sites/cm2 cheek pouch area, respectively. The percentage of postcapillary venules with more than five adherent leucocytes (an index of early leucocyte recruitment) was 1.1 +/- 0.51% in the control situation, and did not increase significantly after stimulation with histamine alone (0.3-10 microM) or with 1 nM leukotriene B4 (LTB4). On the other hand, coapplication of 10 microM histamine and 1 nM LTB4 increased leucocyte adhesion 24-fold. In fact, the 10 times lower dose of histamine (1 microM) together with 1 nM LTB4 increased leucocyte adhesion to a similar extent (20 fold). The increase in vascular permeability evoked by exogenous 10 microM histamine (with or without LTB4), or by histamine released from activated mast cells (antigen challenge), was completely reversed by local pretreatment with the H1-receptor antagonist mepyramine. This mepyramine treatment also abolished the enhanced leucocyte adhesion in response to coapplication of histamine and LTB4. Moreover, mepyramine, which had no effect on leucocyte recruitment evoked by 3 nM LTB4 per se, reduced antigen-induced recruitment of leucocytes to the extravascular tissue by 79.5 +/- 14.8%. CONCLUSION: We conclude that threshold concentrations of histamine can strikingly potentiate chemoattractant-induced leucocyte responses, and that in order to reduce allergic leucocyte recruitment it may be necessary to use antihistamines in doses high enough to abolish the microvascular actions of histamine.

Animals↗
PubMed1995

Microvascular mechanisms of histamine-induced potentiation of leukocyte adhesion evoked by chemoattractants.

1. Intravital microscopy of the rat mesentery was used to examine interactions between histamine and the chemoattractant leukotriene B4 (LTB4) with regard to leukocyte adhesion in postcapillary venules. 2. Topical administration of histamine caused a four fold potentiation of LTB4-induced leukocyte adhesion. 3. Histamine significantly increased the rolling leukocyte flux by 25%, and this effect of histamine on rolling was strictly blood flow-dependent, i.e. we found significant positive correlations between both blood flow and total leukocyte flux and between total and rolling leukocyte flux, while no changes in leukocyte rolling fraction or rolling velocity were observed. Furthermore, histamine caused a clear-cut increase in venular plasma protein leakage. 4. The platelet-activating factor (PAF) receptor antagonist WEB 2086, which effectively inhibited adhesion of leukocytes evoked by exogenous PAF, did not reduce the potentiating effect of histamine on LTB4-induced leukocyte adhesion. 5. The vasodilator acetylcholine (ACh) caused a moderate enhancement of LTB4 induced leukocyte adhesion in proportion to its blood flow-dependent 40% increase in rolling leukocyte flux. In contrast to histamine, ACh did not provoke vascular leakage of plasma proteins. 6. Taken together, our findings suggest that histamine plays an important pro-inflammatory role in tissues where leukocyte rolling is already present, by potentiating chemoattractant-induced firm leukocyte adhesion through a combination of microcirculatory changes such as increased rolling leukocyte flux and vascular permeability.

Amino Acid Sequence↗
PubMed1995

Laser-Doppler perfusion imaging of microvascular blood flow in rabbit tenuissimus muscle.

To evaluate a newly developed high-resolution laser-Doppler perfusion imager (HR-LDPI) for analysis of local tissue perfusion, blood flow measurements in the rabbit tenuissimus muscle were carried out in combination with intravital microscopic observation. The principle of the LDPI method is based on a low-power laser beam scan of the exposed tissue from which a two-dimensional color-coded perfusion map is created through computerized signal analysis. The perfusion of the tenuissimus muscle prepared for microscopic observation was analyzed in a 5 mm x 8 mm area as the muscle was exposed to atmospheric oxygen tension (Po2; 20 kPa), a low Po2 (approximately 3 kPa), and after vasodilatation induced by topical application of prostaglandin E2 (PGE2). In selected areas free from larger vessels, a significantly lower perfusion average reading was demonstrated under high Po2 conditions compared with low Po2 conditions (P < 0.05, n = 5 animals), and application of PGE2 gave rise to an average reading significantly higher than that at low Po2 (P < 0.01, n = 6 animals). The results were in good agreement with the flow changes observed microscopically, and the architecture of the microvascular network, as depicted by in vivo micrographs, was clearly recognizable in the perfusion images. In conclusion, blood flow changes in the rabbit tenuissimus muscle induced by various stimuli were quantitated with the HR-LDPI method and could be spatially resolved in great detail, illustrating the potential of using HR-LDPI for analysis of local blood flow and to reveal spatial perfusion heterogeneity in tissues.

Animals↗
PubMed1994

Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion in postcapillary venules in vivo.

As studied by intravital microscopy, local challenge with the mast cell secretagogue compound 48/80 was found to increase the leukocyte rolling fraction, decrease rolling velocity and induce firm leukocyte adhesion in postcapillary venules of the rat mesentery. These effects of compound 48/80 were inhibited by a monoclonal anti-P-selectin antibody, but not by combined treatment with H1 and H2 histamine-receptor antagonists. Moreover, the response to compound 48/80 was not mimicked by exogenous histamine or 5-hydroxytryptamine (5-HT). These novel findings indicate that mediator(s) other than histamine and 5-HT evoke P-selectin-dependent leukocyte rolling and thereby promote firm leukocyte adhesion in mast cell-dependent inflammation.

Animals↗
PubMed1994

Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis in experimental meningitis in the rabbit.

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute significantly to the neurological damage commonly associated with this serious disease. In this study we tested whether or not inhibition of leukocyte rolling, a precondition for firm leukocyte adhesion to vascular endothelium in vivo, may reduce CSF leukocyte recruitment and associated inflammatory changes in rabbits with experimental meningitis. As documented by intravital microscopy of small venules in the rabbit mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer of sulfated L-fucose known to block the function of the leukocytic "rolling receptor" L-selectin. Moreover, fucoidin treatment dramatically reduced the accumulation of both leukocytes and plasma protein in the CSF of rabbits challenged intrathecally with pneumococcal antigen. These main findings thus illustrate that inhibition of leukocyte rolling, an early and obligatory step in the process of leukocyte extravasation, may be an effective therapeutic approach to attenuate leukocyte-dependent central nervous system damage in bacterial meningitis.

Animals↗
PubMed1992

Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling.

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.

Animals↗
PubMed1991

[Leukocyte adhesion: a fundamental process in immunologic and inflammatory reactions].

Adhesion to cells and extracellular matrices is a fundamental feature of leukocyte physiology, a process crucial to the generation of immune and inflammatory responses. Adhesive interactions between lymphocytes, monocytes/macrophages, granulocytes and vascular endothelial cells are mediated by specific cell-adhesion molecules (CAMs). The Leu-CAMs (CD111/CD18) belong to a large family of cell-surface molecules known as intergrins, a family which also includes receptors for extracellular matrix components. In man, inherited deficiency of Leu-CAMs is characterised by recurrent, sometimes fatal, bacterial infections. In animals, on the other hand, Leu-CAM blocking by monoclonal antibodies has been found beneficial in inflammatory disorders. As some lymphoid malignancies are devoid of CAMs, it is possible that their absence may be a contributing factor in the development of leukaemia and lymphoma.

Antibodies, Monoclonal↗