Acute microvascular effects of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine: comparisons with leukotriene B4

Abstract

Acute effects of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) on microvessels of the hamster cheek pouch were studied using intravital and electron microscopy. FMLP (1.0 microM) applied topically to the pouch microvasculature produced transient vasoconstriction of second- and third-order arterioles, which was accompanied by modest narrowing of pericytic venules, leukocyte adherence, diapedesis, and macromolecular extravasation. Contrary to observations of leukotriene B4 (LTB4)-exposed venules in the same animal model, electron micrographs of fMLP-treated venules supported junctional, vesicular, and potential transcellular modes of transendothelial protein transport. Endothelial junctions were not characterized by large gaps, but failure of endothelial processes to effectively bridge diapedesing cells and reestablish junctional contact resulted in substantial deposition of subendothelial reaction product. Venous microvessels 18-21 micron in diameter were particularly susceptible to the deleterious effects of fMLP and revealed the highest percentage of total junctions or endothelial cells labeled by reaction product. Implied barrier dysfunction was more prevalent in fMLP-treated vessels exhibiting adherence and/or diapedesis; however, the presence of barrier defects was not correlated with leukocyte margination and/or emigration (Marg/Emig). The absence of simple correlation, without persuasive evidence for direct vasopermeability effects, recognizes that some Marg/Emig events may not have been present at the time of fixation and suggests the potential for neutrophil-mediated endothelial dysfunction, governed by multiple determinants, is often unrealized.