Alternative Macrophage Activation-Associated CC-Chemokine-1, a Novel Structural Homologue of Macrophage Inflammatory Protein-1α with a Th2-Associated Expression Pattern

• DOI: 10.4049/jimmunol.160.3.1411
• Publication Date: 2022-12-31T14:12:47Z
• Authors: Vitam Kodelja; Carola Müller; Oliver Politz; Nahid Hakij; Constantin E. Orf...; Sergij Goerdt
• Keywords: Models, Molecular; 0303 health sciences; Interleukin-13; Base Sequence; Sequence Homology, Amino Acid; Molecular Sequence Data; Macrophage Activation; Macrophage Inflammatory Proteins; Interleukin-10; 3. Good health; 03 medical and health sciences; Th2 Cells; Chemokines, CC; Macrophages, Alveolar; Humans; Amino Acid Sequence; Interleukin-4; Cloning, Molecular; Chemokine CCL4; Sequence Alignment

AbstractWe 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-1α 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-1α. While MIP-1α 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-γ 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.