Differential role of neutrophils and monocytes during subcutaneous plasma extravasation

Abstract

We examined the behavior of polymorphonuclear leukocytes (PMNs) and monocytes during subcutaneous plasma extravasation in guinea-pigs. Plasma extravasation was induced by intradermal injection of zymosanactivated plasma (ZAP). The degree of extravasation correlated logarithmically with the concentration of injected ZAP, and was composed of PMN-dependent and -independent components. The latter was mediated primarily by histamine. The former accounted for 40-50% of the total plasma extravasation, peaked within 15 min, and then rectilinearly decreased with a half-life between 30 and 40 min. Histological examination of skin at 15 min after ZAP injection demonstrated PMN attachment to the luminal surface of venule endothelial cells, without evidence of PMN extravasation. We next examined whether monocyte infiltration of subcutaneous tissue played a causal role in plasma extravasation. Monocyte-predominant infiltration was initially caused by an intradermal injection of a monocyte-specific chemotactic factor, the S19 ribosomal protein (RP S19) dimer. Monocyte infiltration did not induce plasma extravasation even in guinea-pigs with elevated peripheral blood monocyte levels following administration of a macrophage-colony stimulating factor. A simultaneous injection of prostaglandin E 2 , a vasodilating agent, with RP S19 dimer also did not induce plasma extravasation. In contrast, a simultaneous injection of RP S19 dimer with ZAP changed the leukocyte infiltration pattern from PMN-predominant to monocyte-predominant, and almost completely suppressed the PMN-dependent component of the ZAP-induced plasma extravasation. The lack of plasma extravasation in the monocytepredominant pattern was reproduced when a strong monocyte infiltration was induced by an intradermal injection of apoptotic cells. We conclude that leukocyte-induced plasma extravasation is specific for PMN, and is not due to a physical leakage of plasma during leukocyte emigration. Rather, plasma extravasation is probably caused by a cognate interaction between PMNs and postcapillary venule endothelial cells.

Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor

“…Using a very different model system, Tokita and Yamamoto 15 recently reported that, upon intradermal injection into the skin of guinea-pigs, necrotic HL-60 cells enhanced local extravasation of plasma whereas apoptotic HL-60 cells had little or no effect. In the present study, we investigated the effects, on local vascular permeability (as assessed by 125 Ifibrinogen extravasation and 125 I-fibrin deposition), of the induction of apoptosis in native dermal MC populations whose numbers had been greatly expanded by the repetitive injection of the MC growth/ survival factor, SCF.…”

The role of the ribosomal protein S19 C-terminus in Gi protein-dependent alternative activation of p38 MAP kinase via the C5a receptor in HMC-1 cells

“…Evans blue dye was used to measure vascular permeability enhancement (VPE) for 30 min (Supplemental Fig. 1) [32]. C5a/RP S19 exhibited the C5aR agonist-induced VPE at relatively high concentrations in comparison with C5a.…”

Roles of leukocytosis and cysteinyl leukotriene in polymorphonuclear leukocyte-dependent plasma extravasation

“…injection of C5a was less marked in bone marrow failure patients [5] and in neutropenic patients [6]. We have demonstrated that PMN-dependent plasma extravasation is specific to PMN infiltration by showing that monocyte infiltration does not accompany plasma extravasation, even in the monocytotic state of peripheral circulation [7].…”

“…In terms of the mechanism of the PMN-dependent plasma extravasation, it was possible that the extravasation was simply a leakage of plasma during the passage of leukocytes at the postcapillary venule wall. However, we recently discarded this possibility when we observed that monocyte infiltration does not accompany plasma extravasation and that the PMN-dependent plasma extravasation occurs before PMN extravasation [7]. This strongly suggests the possibility that the PMN-dependent plasma extravasation is caused by a specific interaction between PMNs and endothelial cells.…”