Production of Superoxide Anion and Hydrogen Peroxide by Human Neutrophilic Granulocytes during Chemotactic Migration towards f-Met-Leu-Phe, C5a, Leukotriene B4, Monocyte-Derived Chemotaxin/IL-8 and Platelet-Activating Factor

Abstract

During the chemotactic migration of human neutrophilic granulocytes towards the chemotactic factors f-Met-Leu-Phe, C5a, leukotriene B₄ (LTB₄), monocyte-derived chemotaxin (MOC/IL-8) and platelet-activating factor (PAF) in Boyden chambers, the production of superoxide anion and hydrogen peroxide was measured by superoxide dismutase-inhibitable cytochrome C reduction and oxidation of p-OH-phenylacetic acid, respectively. With the exception of 10^––⁶M PAF, none of the factors at optimal chemotactic concentrations induced the production of O₂ or H₂O₂ in amounts significantly different from neutrophilic granulocytes migrating at random. At 20–50 times the optimal chemotactic concentration some O₂ and H₂O₂ production was observed with f-Met-Leu-Phe, C5a and LTB₄, but not with MOC/IL-8. Superoxide dismutase, catalase or a combination of the two added to both compartments of the Boyden chambers did not affect the random or chemotactic migration towards any of the chemotactic factors. The results suggest that chemotactic migration and the production of reactive oxygen metabolites by human neutrophilic granulocytes are unrelated events.

Cardiac release of chemoattractants after ischaemia induced by coronary balloon angioplasty.

“…This interaction is facilitated by the prolonged contact between blood cells and endothelial cells under low (or zero) shear stresses and by an accumulation of inflammatory mediators that are neither washed off nor counterbalanced by inflowing endogenous inhibitors.6 Potential mediators of a mutual modification of cell function between blood cells and endothelial cells include platelet activating factor3238 tumour necrosis factor,'9 40 interleukins 6 and 8,28 41 and vasoactive arachidonic acid metabolites.4424 Furthermore, complement 1lq fixation may occur at activated adherent neutrophils resulting in the formation of chemotactic complement fractions.7 30 Consistent with these concepts, cardiac release of vasoactive substances has been shown in patients with coronary artery disease.44 Our study shows, for the first time, a release of chemoattractants with concomitant neutrophil activation in the ischaemic human heart during PTCA. Endothelial cell blood cell interactions with mutual cell activation may, therefore, be assumed to start early during myocardial ischaemia.…”

“…(Br Heart J 1993;70: [27][28][29][30][31][32][33][34] Recent experiments suggest that interactions between leucocytes, platelets, and endothelial cells may cause microvascular injury in myocardial ischaemia. [1][2][3][4] These cell to cell interactions involve an ongoing release of chemoattractants and cytokines57 and a pro-gressive cell activation with discharge of various toxic compounds predominately derived from leucocytes.'…”