Expression of TCR types on gut intraepithelial lymphocytes.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D Befus
Publications and source records attributed to D Befus.
Solute movement across the alveolar-capillary membrane after intratracheally administered bleomycin in rats.
The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Predominance of IgA deposits in glomeruli of Schistosoma mansoni infected mice.
We found that IgA is predominant among the immune deposits in the renal glomeruli of mice infected with Schistosoma mansoni, and thus conducted an analysis of the deposition of different immunoglobulin isotypes in the glomeruli throughout the course of infection in mice. Both immunofluorescent and immunoperoxidase methodologies were employed and compared. The abundance of S. mansoni antigens and the isotypes of antibodies to these antigens were examined in the sera and kidney eluates of mice during the course of infection and the results were related to the findings of immunohistopathology. Our observations suggest that at least some immune complexes form in situ in the glomeruli of infected mice and support a possible role of liver damage in the pathogenesis of renal disease in schistosomiasis. Intestinal mucosal immune responses to schistosome antigens may be important in the evolution of renal disease. In addition, the relevance of the murine model to human schistosomal nephropathy is questioned.
Animals↗
Mast cell pleomorphism: properties of intestinal mast cells.
Explore the source record for details and available documents.
Animals↗
The role of the mast cell in allergic bronchospasm.
In allergic bronchospasm inhaled allergen interacts with specific IgE antibody on the surface of mast cells, inducing the release of mediators, particularly histamine and leukotrienes, which induce bronchoconstriction. Disodium cromoglycate, previously considered to be predominantly a mast cell stabilizing agent, is effective prophylactically in inhibition of early and late phase asthmatic reactions. However, the microenvironment of the airways contains many cell types and the precise role of mast cells is not clear. Lymphocytes, alveolar macrophages, eosinophils, platelets, and neutrophils possess low affinity surface receptors for IgE and can respond to allergen, releasing mediators that have diverse functions. These observations compound the problem of which mediator(s) is most important in pathogenesis of asthma. Moreover, mast cell products modulate the functions of many cells, and thus whether mast cells act directly or indirectly on bronchial smooth muscle requires clarification. Neuropeptides activate or modulate mast cells, and together with evidence of the close association of mast cells and nerves, these observations provide exciting new directions for investigation. Evidence that mast cells from different sites are heterogeneous in their response to stimuli and antiallergic drugs and differ in mediator production and function amplifies the problems identified above. In summary, the role of mast cells in bronchoconstriction is complex and systematic analysis of interactions between mast cells and other cells of the airways is essential.
Asthma↗
Investigations of rat mast cell heterogeneity.
In the rat, two distinct mast cell subsets have been identified. One, represented by the easily accessible and purified peritoneal mast cell, differs from the other, the intestinal mucosal mast cell, in staining properties, fixation sensitivity, mediator content, and responsiveness to various secretagogues and antiallergic drugs. To investigate the molecular basis and control mechanisms of mast cell heterogeneity, we have initiated sodium dodecylsulfate polyacrylamide gel electrophoretic analysis of the constituents of rat peritoneal and intestinal mucosal mast cells; developed subcellular fractionation protocols to facilitate these comparisons; produced a mast cell specific rabbit antiserum, and established methods to isolate mast cell RNA. These approaches require refinement, but will prove to be useful in further investigations of mast cell biology.
Animals↗
Differentiation of parenchymal lung disorders with in vitro proton nuclear magnetic resonance.
We investigated in vitro NMR properties of bleomycin-induced alveolitis and pulmonary fibrosis in 18 Lewis rats (6 controls). When alveolitis or fibrosis had developed, animal lungs were excised and examined histologically and gravimetrically and their T1 and T2 were determined by a NMR spectrometer at 10.7 MHz and 37 degrees C. Clinical diagnosis was confirmed histologically in each case. The NMR signal intensities were significantly elevated in both disease states (P less than 0.001). Both T1 and T2 values of alveolitic lungs were about the same as in controls, but were significantly decreased in fibrotic lungs (P less than 0.01). Changes in T1 and T2 correlated well (P less than 0.001) with changes in water content of diseased lungs.
Animals↗
Immunity in intestinal helminth infections: present concepts, future directions.
Although intestinal helminth and protozoan infections are prevalent throughout the world, their impact is poorly known. Nevertheless, the morbidity and mortality that occur have stimulated research into host resistance and pathogenesis. Unfortunately, despite an increasing knowledge base, the actual effector molecules which lead to parasite loss are unknown. IgA antibody, intraepithelial leukocytes and mucosal mast cells are thought to be involved. The role of these and other responses in making the intestinal microenvironment hostile to the parasite through effects of neurotransmission, epithelial cell differentiation and function, smooth muscle activities, and local inflammatory responses must be studied. Future research will include: further definition of the cellular and molecular immunologic repertoire of the intestine, identification of local effector molecules and investigation of interactions between antigen-specific immune responses and intestinal physiology. Studies of human infections will be more restricted but must include: assessment of parasite-specific local immunologic responses, inflammatory events in the intestine, and development of relatively non-invasive techniques to study gastrointestinal physiology during parasitic infection. Perhaps most importantly, research facilities must be established in developing countries to investigate intestinal immunological, inflammatory and physiological responses during infection. Through such investigations, risk factors for susceptibility and disease severity may be identified and therapeutic or prophylactic strategies developed.
Animals↗
Unique characteristics of local responses in host resistance to mucosal parasitic infections.
Because of the tremendous impact that parasitic infections have on the health and productivity of humans and domestic animals, considerable research effort has been focused upon understanding the mechanisms of host-parasite coexistence, host resistance and immunopathology. Studies have employed a range of approaches including: kinetic analysis of parasite establishment, development, fecundity and survival in naive and previously-infected hosts; correlation between parasite survival and histopathologic responses at the site of infection; vaccination with attenuated parasites or their products; cellular and serum transfer of immunity to naive or immunocompromised hosts; pharmacologic manipulation of potential mediators of host defense using agonistic and antagonistic drugs. However, it is becoming increasingly clear that to understand the mechanisms associated with host resistance and parasite survival, one must define the characteristics of the local microenvironment at the host-parasite interface. One of the approaches by which such studies can be made involves the isolation and characterization of cells derived from the local infection site. This manuscript reviews some of these studies on local aspects of mucosal immune responses in parasitic infections. Examples that will be discussed include IgA antibody, intraepithelial leukocytes from the intestine, intestinal mast cell populations, macrophages derived from bronchoalveolar lavage, and local immunoregulatory responses during respiratory and intestinal parasitic infection. These studies have established unequivocally that local responses to mucosal parasitic infection can only be appropriately investigated using cells derived from the specific microenvironment. This conclusion should encourage others to further study these local responses and to be innovative in investigating unexplored aspects of the host-parasite interface.
Animals↗
Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen.
We examined the effect of vasoactive intestinal peptide, substance P, and somatostatin on concanavalin A (1 microgram/ml)-induced lymphocyte proliferation and immunoglobulin (IgA, IgM, and IgG) synthesis by cells from spleens, Peyer's patches, and mesenteric lymph nodes. These neuropeptides (10(-7) to 10(-12) M) modulated immune responses in a dose-dependent manner. For a comparative study, neuropeptides were used at 10(-8) M concentration. Both vasoactive intestinal peptide and somatostatin significantly decreased DNA synthesis (30 to 50%), whereas substance P increased synthesis (40%) in lymphocytes from all organs tested. IgA synthesis was significantly altered by all of the neuropeptides tested, whereas IgM synthesis was less affected and IgG synthesis was virtually unchanged. Somatostatin inhibited IgA (20 to 50%) and IgM (10 to 30%) synthesis in lymphocytes from all three organs. Substance P increased IgA synthesis in mesenteric lymph nodes (50%), spleens (70%), and Peyer's patches (300%). It also increased IgM synthesis in Peyer's patches (20%) and spleens (30%), but was without effect on IgM synthesis in mesenteric lymph nodes. Vasoactive intestinal peptide increased the IgA response in mesenteric lymph nodes (20%) and spleens (30%), but inhibited IgA synthesis in lymphocytes from Peyer's patches (60%). Interestingly, in Peyer's patches, IgM synthesis was increased by vasoactive intestinal peptide (80%), whereas it was unchanged in mesenteric lymph nodes and spleen. Thus, not only did these neuropeptides have different effects on the production of different immunoglobulin isotypes, but their effect was also organ-specific. Because neuropeptides which are abundant in the intestine can modulate IgA and other immunoglobulin synthesis in vitro, they may play a significant regulatory role in mucosal immune responses in vivo.
Animals↗
Peripheral blood basophils, basophil progenitors, and nasal metachromatic cells in allergic rhinitis.
Relationships among mature blood basophils, blood basophil colony-forming units in culture (CFU-c), and nasal metachromatic cells (NMC) were investigated using hemopoietic and histochemical techniques in 29 patients with allergic rhinitis and in 7 nonatopic control subjects. Total blood granulocyte and basophil CFU-c were significantly elevated in atopy; the highest levels of basophil CFU-c were found in patients with low total NMC counts in nasal scrapings (Group I), compared with those with intermediate (Group II) or high (Group III) counts: 10 +/- 3 basophil CFU-c per 10(6) cells in 10 Group I patients, 4 +/- 2 in 10 Group II patients, 3 +/- 1 in 9 Group III patients, and 0.1 +/- 0.1 in nonatopic control subjects (p less than 0.05). Mean histamine content and frequency of histamine-positive granulocyte colonies correlated with counts of basophils in colonies (r = 0.864, p less than 0.001). Peripheral blood basophils, which stained metachromatically with toluidine blue at pH 0.5 after Mota's lead acetate but not after formalin fixation, were highest in atopic Group III and lowest in Group I; a similar relationship was observed only for NMC, which also failed to stain after formalin fixation. Metachromatic cells in colonies were similar to formalin-sensitive NMC and to peripheral blood basophils in their sensitivity to different fixatives. Nasal symptoms correlated inversely with the number of basophil CFU and directly with the number of either formalin-sensitive NMC or peripheral blood basophils. These findings confirm and extend evidence for increased nasal metachromatic cells, basophilia, and alterations in basophilopoiesis in atopy.
Adolescent↗
Heterogeneity of metachromatic cells in human nose: significance of mucosal mast cells.
The distribution and abundance of histochemically and morphologically distinct subpopulations of metachromatic cells were investigated in nasal secretions and scrapings from patients with allergic rhinitis, as well as in nasal biopsy specimens from other patients. These analyses of the metachromatic cells demonstrate that basophils and two distinct mast cell populations are present in nasal specimens. One mast cell subpopulation was analogous to the atypical mucosal mast cell of the rat and human intestine, whereas the other cell population was similar to the typical connective tissue mast cell type. In nasal scrapings greater than 80% of the metachromatic cells was mast cells, almost exclusively of the atypical "mucosal" type. However, basophils were the predominant metachromatic cell type in nasal secretions, and atypical mast cells were more abundant than typical mast cells. Few basophils were observed in biopsy specimens, but mast cells were widely distributed in various anatomic compartments. Atypical mast cells outnumbered the typical type in the epithelium and lamina propria, whereas the reverse was true in the submucosa. When the number and type of metachromatic cell in scrapings were analyzed in relation to clinical findings, there was a significant correlation with severity of symptomatology and nasal swelling and pallor. Atypical "mucosal" mast cells were the major cell type in all specimens, from those with mild to those with severe clinical findings. When the distinct spectrum of responsiveness to antiallergic compounds of atypical mast cells is considered, these observations have important therapeutic implications.
Adolescent↗
Mast cell heterogeneity in man. I. Histologic studies of the intestine.
We have studied the distribution and abundance of histochemically distinct mast cell subpopulations in the normal small and large intestine of man. One subpopulation has histochemical properties similar to the functionally distinct intestinal mucosal mast cell (MMC) of the rat and the other has properties similar to the widely distributed mast cell found in connective tissues and the peritoneal cavity of many animals. Both subpopulations are present in intestinal epithelium, lamina propria, submucosa and muscularis mucosa, and muscle. However, the subpopulation histochemically similar to the rodent MMC is significantly more abundant than the other in all sites in the large intestine and also in the lamina propria and muscle of the small intestine. It is important to determine whether these histochemically distinct mast cell subpopulations in man differ in their responses to various secretagogues and antiallergic compounds as in the rat.
Cell Count↗
Comparative aspects of mast cell heterogeneity in different species and sites.
Explore the source record for details and available documents.
Animals↗
Mast cell heterogeneity: effects of neuroenteric peptides on histamine release.
Recent reports suggesting that the actions of certain neuroenteric peptides may be mediated in part by the secretion of histamine and other mast cell contents could have important implications for gastrointestinal motility and secretion. However, evidence for a mast cell-hormonal interaction is based on studies using peritoneal or cutaneous mast cells. Because intestinal mucosal mast cells (MMC) differ functionally from peritoneal mast cells (PMC), we compared the effects of several neurotransmitters and intestinal hormones on histamine secretion from two mast cell types in the rat. MMC hyperplasia was induced in rats by infection with the nematode Nippostrongylus brasiliensis, and MMC were isolated from the small intestine by collagenase digestion. Substance P, somatostatin, vasoactive intestinal polypeptide (VIP), neurotensin, and bradykinin had a potent secretagogue effect on (10(-7) to 10(-4)M) PMC which was temperature-, energy-, and calcium-dependent. In contrast to PMC, MMC released significant amounts of histamine only when challenged with substance P. Acetylcholine, bombesin, motilin, and pentagastrin had no secretory effect on either PMC or MMC. The differences between PMC and MMC in responsiveness to peptides could not be attributed to the MMC isolation procedure because PMC treated similarly or mixed with MMC suspensions retained their responsiveness to these stimuli. Our results extend the concept of neurocrine control of mast cell function, but indicate that mast cells from different sites have distinct profiles of responsiveness to regulatory peptides.
Animals↗
Gut- and bronchus-associated lymphoid tissue.
Bronchus-associated and gut-associated lymphoid tissues (BALT and GALT) have both functional and morphologic similarities and are involved in seeding lung, gut, and other mucosal sites with predominantly IgA-containing B cells. Both types of lymphoid tissue are engaged in the regulation and the controlled amplification of immune responses, which vary from positive mucosal responses in both mucosae and peripheral tissues to local mucosal responses and systemic tolerance. Their further involvement in provision of cells destined to reside in the epithelial compartment of the body appears likely but requires further investigation. Their role in the provision of precursors of mucosal mast cells must also be explored further, but some participation in this event appears likely. The mucosa-associated lymphoid tissue (MALT) system appears to be integrated with the systemic immune system but may be considered as separate from it in several functional ways.
Animals↗
Induction and expression of mucosal immune responses and inflammation to parasitic infections.
Explore the source record for details and available documents.
Antigens↗
Broncho-alveolar leucocyte responses during primary and secondary Nippostrongylus brasiliensis infection in the rat.
Using broncho-alveolar lavage, we have studied the cellular responses in the rat lung following primary and secondary infection with Nippostrongylus brasiliensis. During the primary infection, there was a biphasic increase in total broncho-alveolar leucocytes and in the absolute numbers of macrophages, neutrophils, eosinophils and lymphocytes. The first peak occurred on days 4-6, and the second peak occurred around day 16, after infection. During the secondary infection there was an anamnestic-like response by all cell types. These data suggest that the broncho-alveolar leucocyte responses to infection have an immunological basis and that in addition to the alveolar macrophage, neutrophils, eosinophils and lymphocytes may play a significant role in lung resistance against migrating helminth larvae.
Animals↗