Diapedesis and the permeability of venous microvessels to protein macromolecules: the impact of leukotriene B4 (LTB4).
The cellular basis of the reported neutrophil-dependent increase in microvascular permeability evoked by leukotriene B4 (LTB4) was probed using protein intravascular fluorescent and electron dense tracers in conjunction with intravital, light and electron microscopy. LTB4 (1 microM) applied topically to the hamster cheek pouch promoted neutrophil (PMN) adherence to endothelial cells (ECs) and resulted in limited, diffuse leakage of fluorescein-labeled albumin from pericytic venules. ECs to which PMNs adhered displayed many vesicles and a prominent cytoskeletal reorganization of microfilaments. During emigration, microfilament-rich luminal extensions of ECs effectively resealed the endothelial barrier prior to or in conjunction with PMN penetration of the basal lamina. Intimate associations between PMNs and ECs, coupled with efficient bridging of the lumen by EC processes, argued against significant transendothelial escape of macromolecules concomitant with PMN egress. Studies employing horseradish peroxidase as an intravascular tracer suggested minimal enhancement of junctional permeability in small venules and refuted a role for vesicular transport. The primary apparent barrier defect was a selective alteration in the membrane integrity of a proportion of ECs.
Lewis
R E
RE
Microcirculation Research Institute, Texas A&M University, College Station 77843.
Granger
H J
HJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D009504:Neutrophils / Q000502:physiology* / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D007975:Leukotriene B4