title: Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern.
abstract: We have cloned a novel human CC-chemokine, alternative macrophage activation-associated CC-chemokine (AMAC)-1. The isolated cDNA clone (803 bp) shows a single open reading frame of 267-bp coding for 89 amino acid residues; mature AMAC-1 protein is predicted to consist of 69 amino acids with a m.w. of 7855. Sequence alignment and 3D-modeling show the typical structural characteristics of CC-chemokines with special features in the receptor-activating domain. AMAC-1 is most closely related to MIP-1 alpha with a cDNA and protein sequence homology of 55% and 59%, respectively. However, the expression pattern of AMAC-1 is directly opposite to that of MIP-1 alpha. While MIP-1 alpha is induced by classical macrophage mediators such as LPS and is inhibited by IL-4 and glucocorticoids, AMAC-1 is specifically induced in macrophages by alternative macrophage mediators such as IL-4, IL-13, and IL-10. Expression of AMAC-1 is inhibited by IFN-gamma while glucocorticoids exert a slightly positive synergistic effect in combination with IL-4. Peripheral blood monocytes do not express AMAC-1; time course experiments show that monocyte-to-macrophage differentiation is a prerequisite for AMAC-1 expression. Expression of AMAC-1 by granulocyte-macrophage CSF/IL-4-induced, monocyte-derived dendritic cells is complex; in mature adherent dendritic cells, however, only minor AMAC-1 mRNA expression was found. In vivo, AMAC-1 is expressed by alveolar macrophages from healthy persons, smokers, and asthmatic patients. In conclusion, AMAC-1 is a novel CC-chemokine whose expression is induced in alternatively activated macrophages by Th2-associated cytokines; thus, AMAC-1 may be involved in the APC-dependent T cell development in inflammatory and immune reactions.
authors.affiliation: Klinik und Poliklinik für Dermatologie, Universitätsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kodelja
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: O
authors.initials: O
authors.lastname: Politz
authors.forename: N
authors.initials: N
authors.lastname: Hakij
authors.forename: C E
authors.initials: CE
authors.lastname: Orfanos
authors.forename: S
authors.initials: S
authors.lastname: Goerdt
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D003001:Cloning, Molecular; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008262:Macrophage Activation; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: C111792:CCL18 protein, human; D054407:Chemokine CCL4; D019742:Chemokines, CC; D018793:Interleukin-13; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D015847:Interleukin-4