Leukocyte-induced vascular protein leakage in cat mesentery.
The overall objective of this study was to determine whether leukocyte adherence and/or emigration is a prerequisite for the increased vascular protein leakage associated with acute inflammation. An in vivo preparation was used to monitor intestinal vascular protein leakage as well as polymorphonuclear leukocyte (PMN) adhesion and emigration in feline mesenteric microvessels exposed to platelet-activating factor (PAF) and leukotriene B4 (LTB4). Local intra-arterial infusion of PAF (4 ng/min) produced a fourfold increase in vascular protein leakage. A 50-fold higher concentration of LTB4 had no effect on vascular protein efflux. LTB4, however, did potentiate the PAF-induced vascular protein leakage. Both inflammatory mediators caused leukocytes to adhere to endothelial cells in postcapillary venules; however, leukocyte emigration was observed only in the presence of PAF. PAF-induced leukocyte adhesion and emigration and the increased vascular protein leakage were inhibited by a monoclonal antibody (MoAb IB4) directed against the common beta-subunit of the adhesive glycoprotein complex CD11/CD18. MoAb IB4 also prevented LTB4-induced leukocyte adhesion. Both PAF and LTB4 caused degranulation of cat PMNs in vitro, yet superoxide production was stimulated by PAF only. The data derived from these in vivo and in vitro studies indicate that leukocyte adhesion per se does not necessarily lead to increased vascular protein leakage and leukocyte emigration. Adhesion-dependent PMN functions such as emigration and superoxide production may play an important role in producing the alterations in vascular integrity observed in inflamed microvessels.
Kubes
P
P
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932.
Grisham
M B
MB
Barrowman
J A
JA
Gaginella
T
T
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002199:Capillary Permeability; D002415:Cats; D002448:Cell Adhesion; D002465:Cell Movement; D007975:Leukotriene B4 / Q000494:pharmacology; D008643:Mesentery / Q000098:blood supply*; D008833:Microcirculation / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D010972:Platelet Activating Factor; D011506:Proteins; D007975:Leukotriene B4