SERUM PROTECTS AGAINST AZUROPHIL GRANULE DEPENDENT DOWN-REGULATION OFCOMPLEMENT-RECEPTOR-TYPE-1 (CR-1) ON HUMAN NEUTROPHILS

Citation
J. Lundahl et al., SERUM PROTECTS AGAINST AZUROPHIL GRANULE DEPENDENT DOWN-REGULATION OFCOMPLEMENT-RECEPTOR-TYPE-1 (CR-1) ON HUMAN NEUTROPHILS, Inflammation research, 44(10), 1995, pp. 438-446
Citations number
62
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
ISSN journal
10233830
Volume
44
Issue
10
Year of publication
1995
Pages
438 - 446
Database
ISI
SICI code
1023-3830(1995)44:10<438:SPAAGD>2.0.ZU;2-0
Abstract
We have investigated the effect of gradual degranulation on the expres sion of functional receptors (CR1 and CR3) on human neutrophils. Incub ation with increasing concentrations of fMLP (10(-10)-10(-7) M) transl ocated CR1 and CR3 to the cell surface in a similar kinetic pattern. W hen reaching maximal expression of receptors (10(-7) M fMLP), 78 +/- 1 0% and 87 +/- 9% of the total pool of CR1 and CR3, respectively, were translocated to the cell surface. To drive the mobilization process fu rther, cytochalasin B was introduced to increase the stimulatory effec t of fMLP. No further increase in CR1 surface expression was obtained. However, we found a characteristic time course of surface appearance of CR1 and CR3 with a maximal surface expression within 1 minute, foll owed by a time-related down-regulation of CR1 but not CR3. In addition , the total pool of CR1 in cytochalasin B treated neutrophils was redu ced after 15 minutes stimulation with fMLP measured by how cytometry a nd immunoblotting, indicating degradation of CR1. The down-regulation of CR1 was concomitant with a translocation of azurophil granules, in terms of upregulation of CD63. Azurophil, but not specific nor secreto ry, granule fractions caused a down-regulation of CR1 on fMLP activate d neutrophils. The presence of human sera and serine protease inhibito r protected CR1 from down-regulation, Together, these findings indicat e that intracellular stored proteases, released in the late part of th e sequential mobilization process, alters the expression of functional receptors mobilized in the early part of the mobilization process. Th e findings also focus on the importance of the microenvironment for th e net outcome of neutrophil activation in terms of functional receptor expression.