The chemokine receptor CCR5 and to a lesser extent CCR3 and CCR2b have been shown to serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry into blood- or tissue-derived macrophages. Therefore, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in monocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by their concentrations of extracellular p24 antigen and levels of intracellular HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetectable throughout maturation of adherent monocytes over 10 days. CXCR4 RNA and membrane antigen were strongly expressed in newly adherent monocytes, but their levels declined at day 7. The amounts of CCR5 RNA remained stable, but the amounts of CCR5 antigen increased from undetectable to peak levels at day 7 and then declined slightly at day 10. Levels of susceptibility to laboratory (HIV-1BaL) and clinical strains of HIV-1 showed parallel kinetics, peaking at day 7 and then decreasing at days 10 to 14. The concordance of levels of HIV DNA and p24 antigen suggested that the changes in susceptibility with monocyte maturation were at or immediately after entry and correlated well with CCR5 expression and inversely with CXCR4 expression.

The mechanisms of human immunodeficiency virus (HIV) infection of a man (VH) homozygous for the

IntroductionMast cells (MCs) and basophils are histamine-containing, metachromatic granulocytes that express the high-affinity IgE receptor, Fc⑀RI, on their surfaces. 1,2 When activated via this receptor, both populations of cells immediately exocytose their granule constituents and then more slowly generate and release cytokines, chemokines, and arachidonic acid metabolites. Thus, these granulocytes play extremely important roles in IgE-mediated inflammatory responses. Although human MCs and basophils are similar in certain aspects, their substantial biochemical and morphologic differences in normal individuals have led to the concept that the 2 populations of cells probably are developmentally unrelated. MCs, for example, reside in tissues and generally possess a centrally positioned, oval nucleus. In contrast, basophils generally reside in the blood and contain a segmented nucleus. The MCs in the lung and skin of most normal individuals contain chymase, carboxypeptidase A, elastase, cathepsin G, and multiple tryptases in their granules. [3][4][5][6][7][8][9][10][11][12][13] Basophils in the peripheral blood of most normal individuals contain cathepsin G and elastase 4 but lack carboxypeptidase A and chymase. 14,15 Tryptase has been detected in normal human basophils. However, in the initial reports, Schwartz and coworkers concluded that normal human MCs contain on average about 250-fold more tryptase protein 16 and about 50 000-fold more tryptase messenger RNA (mRNA) 15 than normal human basophils.Although it was originally thought that the phenotype of a MC was fixed and irreversibly predetermined before its progenitor exited the bone marrow, it is now apparent that human and mouse 26 The developmental relationship between basophils and MCs remains unclear, in part, because no defined biochemical marker has been identified that can distinguish these 2 populations of cells in an animal that can be experimentally manipulated. A population of Fc⑀RI ϩ /metachromatic cells that possesses segmented nuclei is present in the peripheral blood of helminth-infected mice. Because of their location and nuclear profiles, it was originally thought that these mouse cells were basophils; however, recent studies have shown that they are actually senescent MCs trafficking from the jejunum to the spleen. 27 We have described a population of cells with both MC and basophil features in the blood of patients with asthma, allergy, and allergic drug reactions. 28 For personal use only. on May 10, 2018. by guest www.bloodjournal.org From cells resemble normal mature basophils in terms of their peripheral blood location, segmented nuclei, and surface expression of the Bsp-1 epitope. However, they more closely resemble normal mature MCs in terms of their surface expression of CD117 (c-kit) and their granule expression of multiple proteases.In the current study, we present additional biochemical evidence that the unusual population of metachromatic cells we identified in the blood of patients with various allergic disorders belongs in...