- 作者: Liang Zhang; James C. Gay; Denis Engilish; Burton R. Andersen
- 作者服務機構: a Departments of Medicine and; Microbiology/Immunology, University of; Illinois at Chicago, College of Medicine and; the West Side VA Medical Center, Chicago, Ill., b The Division of Pediatric; Hematology/Oncology, Department of; Pediatrics, Vanderbilt University Medical; Center, Nashville, Tenn., and; c Methodist Hospital of Indiana and the; Indiana University, School of Medicine, Indianapolis, Ind., USA
- 中文摘要: --
- 英文摘要: The principal sulfatide of virulent Mycobacterium tuberculosis, sulfolipid-I (SL-I), both directly stimulates neutrophil superoxide (O2-) release and, at sub- stimulatory concentrations, primes these cells for markedly enhanced oxida- tive responsiveness to other stimuli. The present study was undertaken to clar- ify the priming mechanisms by comparing cellular events following priming doses of SL-I with those following priming with N-formyl-methionyl-leucyl- phenylalanine (FMLP). We compared the involvement of the calcium cation (Ca2+), as well as membrane protein kinase C (PKC) activity and the transloca- tion of NADPH oxidase-cytosolic cofactor effected by priming levels of the two agonists. The investigation led to two important conclusions. First, we clearly demonstrate that priming by both SL-I and FMLP results from activa- tion of cellular processes that are not involved in direct oxidative activation. For example, whereas direct induction of O2- generation by FMLP and SL-I required increases in intracellular Ca2+, an increase in intracellular calcium concentration ([Ca2+]i) above basal levels was not required for priming. Sec- ond, we identified key differences in the cellular responses to priming doses of SL-I and FMLP. Whereas increased membrane PKC activity caused by prim- ing doses of FMLP was only partially blocked by chelation of intracellular Ca2+, Ca2+ chelation completely inhibited the increase in membrane PKC activity caused by SL-I. NADPH oxidase-cytosolic factor translocation to plasma membranes was completely blocked by pertussis toxin when priming doses of SL-I were used. This guanine-nucleotide-binding protein inhibitor had no effect on FMLP-dependent translocation of the oxidase cofactors. The comparative approach introduced in this report provides a valuable and novel method to discern the complex interactions of various cellular processes that regulate the state of activation of stimulated cells.
- 中文關鍵字: --
- 英文關鍵字: Mycobacterium tuberculosis; Intracellular calcium; NADPH oxidase; Protein kinase c