CC chemokines induce neutrophils to chemotaxis, degranulation, and alpha-defensin release.
We have previously shown that a Taiwanese cohort of HIV-uninfected individuals was associated with the significantly elevated levels of serum beta-chemokines, macrophage inflammatory protein (MIP-1)-alpha and MIP-beta, and RANTES. In the present study, we report that the members of this cohort have significantly greater numbers of lower buoyant-density neutrophils in their blood, which leads to further investigation of the effects of beta-chemokines on neutrophils. By electron and confocal microscopic techniques and FACScan, the results demonstrated that MIP-1alpha, MIP-beta, and/or RANTES readily activated the cells to release a large quantity of alpha-defensins in vitro through the degranulation process, which was the cause of low-buoyant-density neutrophil production. The purified neutrophils underwent chemotaxis and increased phagocytic capability when beta-chemokines were present. Only when using all 3 neutralizing antibodies for CCR1, CCR3, and CCR5 could the chemotaxis of neutrophils be inhibited completely, suggesting that these receptors are involved in transducing activating signals. Because neutrophils are the most abundant white blood cells that can be activated simultaneously to release alpha-defensins and because these proteins are antiviral, including anti-HIV, our results support the hypothesis that in addition to beta-chemokines, the innate immunity of the cohort plays a role in inhibiting the transmission of HIV.
Jan
Ming-Shiou
MS
Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Huang
Yi-Hsien
YH
Shieh
Biehuoy
B
Teng
Ru-Hsiu
RH
Yan
Yao-Pei
YP
Lee
Yuan-Ti
YT
Liao
Ko-Kaung
KK
Li
Ching
C
D015550:Cell Degranulation; D019742:Chemokines, CC / Q000097:blood*; D002634:Chemotaxis, Leukocyte; D005434:Flow Cytometry; D006801:Humans; D009504:Neutrophils / Q000502:physiology* / Q000648:ultrastructure; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000097:blood; D019707:Receptors, Chemokine / Q000097:blood; D023084:alpha-Defensins / Q000097:blood / Q000378:metabolism*
C515300:CCR1 protein, human; C515334:CCR2 protein, human; D019742:Chemokines, CC; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D023084:alpha-Defensins