Cyclical binding, processing, and functional interactions of neutrophils with leukotriene B4

✍ Scribed by Joseph T. O'Flaherty; Jimmy F. Redman; David P. Jacobson

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 1016 KB
• Volume: 142
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041420212

✦ Synopsis

Abstract

Leukotrene (LT) B~4~ activates human polymorphonuclear neutrophils. (PMN) by binding to plasmalemmal receptors. It stimulates PMN to raise cytosolic calcium and degranulate. Both responses end within 15–30 sec. However, in < 15 sec, LTB~4~‐treated PMN lose the ability to respond further to LTB~4~; decrease the affinity and number of high affinity receptors available for binding LTB~4~ sequester LTB~4~ in plasmalemma‐associated sites that are inaccessible to a releasing buffei regi i men; and begin internalizing LTB~4~. Over the next 90 min, the cells increasingly internalize LTB~4~ and convert it to less potent metabolites; release the metabolites; recover LTB~4~ binding sites; and become fully sensitive to LTB~4~. Contrastingly, during the entire 90 min incubation with LTB~4~. PMN retained the capacity to bind and respond normally to a second stimulus platelet‐activating factor. We therefore suggest the following model. LTB~4~ receptors, when ligand‐bound, initiate function but rapidly lose this capacity as they lower their ligand binding affinity and sequester, internalize, or otherwise uncouple from transducing elements. These LTB~4~ receptor changes contribute to terminating PMN responses and producing a stimulus‐selective state of desensitization. During the desensitization period, PMN progressively process and metabolize LTB~4~. This removes LTB~4~ from the environment, thereby allowing PMN to recover functional receptors for and sensitivity to the ligand.