Biomedical subjects

V Carl

Publications and source records attributed to V Carl.

4 recordsLinked to original sources

PubMed1995

PMNs primed for superoxide release and increased CD11b expression do not sequester in normal lung.

Our previous work has implicated platelet activating factor (PAF)-induced neutrophil (PMN) priming and increased CD11b/CD18 receptor expression in the pathogenesis of lung injury following gut ischemia/reperfusion (I/R). In this model CD11b blockade abrogates lung injury but does not alter PMN priming or pulmonary leukosequestration. We, therefore, hypothesized that PAF-stimulated PMN priming and CD11b expression are insufficient to promote lung PMN sequestration. Normal rat PMNs, labeled with 51Cr, were incubated with PAF (10 ng/ml) to induce priming for superoxide (O2-) generation and enhance CD11b expression. Gut I/R animals underwent superior mesenteric artery occlusion for 45 min. 51Cr-labeled PMNs (2 x 10(7)) were injected iv. Study groups, consisting of (a) normal/control, (b) sham/laparotomy, and (c) gut I/R, were given either normal or PAF-treated PMNs. PAF-primed PMNs had increased 2- release and CD11b expression, but did not sequester in the lungs of normal rats. However, following gut I/R PAF-treated PMNs sequestered in the pulmonary bed. These data suggest that PAF priming for O2- generation and increased CD11b expression are insufficient alone to promote PMN sequestration in the lung. Rather, additional factors generated by gut I/R are necessary for this process.

Animals↗

PubMed1994

Lipopolysaccharide-induced CD11B-mediated neutrophil-endothelial adhesion is not required for polymorphonuclear cell priming.

Previous work has implicated both neutrophil-endothelial cell (PMN-EC) adhesion and PMN priming (enhanced superoxide production following activation) in the development of postinjury adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). CD11B, a member of the integrin family of PMN surface receptors, has been alleged to have a prominent role in these inflammatory PMN-EC processes. The purpose of the present study was to test the hypothesis that CD11B-mediated PMN-EC adhesion is necessary for endotoxin (LPS)-induced PMN priming. Human neutrophils, isolated by Percoll gradient centrifugation, were exposed to LPS (100 ng/mL). At fixed times over 120 minutes (a) superoxide following fMLP activation (i.e., priming), (b) PMN-EC adhesion, and (c) expression of CD11B were assayed. Superoxide production was measured by cytochrome c reduction, PMN-EC adhesion with indium-labelled PMN adherence to human umbilical vein endothelial cell (HUVEC) monolayer cultures, and CD11B expression with fluorescent labelled anti-CD11B (60.1) antibodies. The PMN-EC adhesion was biphasic, with an early maximum at 15 minutes followed by a nadir at 60 minutes and secondary rise through 120 minutes of LPS exposure. CD11B expression changed dramatically in temporal association with early PMN-EC adhesion, but the secondary increase in adhesion was associated with only a mild rise in CD11B expression. PMN priming increased after a latency of 15 minutes to a maximum of 800 nmol/10(6) cells/min after 60 minutes of LPS exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗

PubMed1992

Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes.

Complement receptor 1 (CR1) on primate red blood cells (RBC) binds most complement-fixing immune complexes in the circulation. It has been postulated that by binding them, RBC keep immune complexes in the intravascular space and deliver them to the tissue macrophages of the mononuclear phagocyte system. We have developed an in vitro model to study the transfer of RBC-bound immune complexes (heat-aggregated IgG and DNA-anti-DNA) to phagocytic cells (human monocytes). Transfer of immune complexes from RBC to monocytes occurred significantly more rapidly than monocyte uptake of the same immune complexes from solution. In the transfer process, complex-bearing RBC were not bound or sequestered by the monocytes. To define the monocyte receptors involved in binding immune complexes from the RBC surface, monocyte receptors were blocked with MoAbs (anti-CR1, anti-FcRII) or EDTA (to block CR3). Monocyte binding of immune complexes primarily used CR1 with a small contribution from FcRII, and with little or no contribution from CR3 and FcRI. Uptake of immune complexes from solution employed the same monocyte receptors as binding of complexes from the RBC surface. Immune complexes in solution bound to RBC and to monocytes with equally high avidity (approximately 1 x 10(11) l/M), but monocytes expressed a 15-20-fold greater number of immune complex binding sites. We propose that immune complexes distribute between RBC and monocytes according to the binding capacity of these cells, such that at equal or high RBC/monocyte ratios as would be seen in the circulation immune complexes bind to RBC, but at low RBC/monocyte ratios (as would be seen in the sinusoidal circulation of the liver and spleen), most immune complexes bind to monocytes. To define the pathway by which immune complexes move from RBC to monocytes, their release from RBC CR1 was examined. Under various conditions, the dissociation rate was extremely slow, and did not increase with the addition of monocyte supernatants. To examine whether factor I-mediated processing of immune complexes enhances binding of immune complexes to monocytes, RBC-bound complexes were released with factor I, and binding of these 'processed' immune complexes to monocytes was examined. Monocyte binding of these processed immune complexes was slower than of control ones; furthermore, performance of transfer experiments at 4 degrees C, which significantly shows enzymatic processes, did not decrease the rate of immune complex transfer from RBC to monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

PubMed1989

Binding of model immune complexes to erythrocyte CR1 facilitates immune complex uptake by U937 cells.

The E C3b/C4b receptor (CR1) has been shown to rapidly bind large complement-fixing immune complexes (IC) both in vivo and in vitro. It has been proposed that E (RBC) CR1 act as a shuttle mechanism, binding circulating IC and transporting them to tissue macrophages, thereby preventing their deposition in target tissues. In this study we have established an in vitro model system with which to study the transfer of model IC from CR1 on the RBC surface to phagocytic cells. Aggregated IgG (AHG) was opsonized with C3b, bound to RBC CR1, and the binding of these RBC-bound IC by a human monocyte cell line (U937 cells) was examined. U937 binding of AHG from the RBC surface was complete within 2 min, whereas binding of the same AHG from solution required 30 to 60 min. Despite the difference in kinetics of binding, the total amount of IC bound by U937 cells at equilibrium was the same for RBC-bound AHG and for AHG in solution. The transfer of AHG from the RBC to the U937 cell did not require exogenous factor I and was not accompanied by binding of RBC to U937 cells or by erythrophagocytosis. Our data lend support to the hypothesis that binding of IC to RBC CR1 may facilitate the clearance of IC from the circulation by enhancing their uptake by phagocytic cells.

Antibodies, Anti-Idiotypic↗