title: Macrophage-induced rat mesangial cell expression of the 24p3-like protein alpha-2-microglobulin-related protein.
abstract: During screening of a murine macrophage cDNA repertoire for factors potentially able to modulate glomerular cell responses to injury, we identified a gene coding for the murine protein 24p3 lipocalin. Immunostaining of normal rat kidney sections showed positive 24p3-like staining in distal tubules/collecting ducts and small muscular arteries. Although most glomeruli were negative, some did exhibit small numbers of positively stained cells. Cultured rat glomeruli and glomerular mesangial cells secreted the 24p3-like protein in response to macrophage-conditioned medium (MPCM) and the cytokine IL-1beta. MPCM derived from TGFbeta-pretreated macrophages enhanced mesangial cell 24p3 secretion. In contrast, addition of anti-IL-1beta neutralising antibody to MPCM or IL-1beta resulted in suppression of 24p3 secretion. Co-culture of mesangial cells with varying numbers of non-LPS-treated macrophages resulted in dose-dependent secretion of 24p3 into culture supernatants. Archival sections from polyvinyl alcohol-treated and cholesterol-fed rats showed positive glomerular staining for 24p3 in and around glomerular foam cells. Nucleotide sequencing of rat mesangial cell-derived 24p3 cDNA revealed it to be identical to rat alpha-2-microglobulin-related protein (alpha2microGRP), the rat homologue of murine 24p3. These data provide the first description of rat alpha2microGRP in the context of mesangial cell pathophysiology.
authors.affiliation: Department of Nephrology, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. iap l@le.ac.uk
authors.forename: Izabella Z A
authors.initials: IZ
authors.lastname: Pawluczyk
authors.forename: Peter N
authors.initials: PN
authors.lastname: Furness
authors.forename: Kevin P G
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D003470:Culture Media; D018076:DNA, Complementary / Q000737:chemistry; D005260:Female; D005920:Glomerular Mesangium / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D000906:Antibodies; D003470:Culture Media; D018076:DNA, Complementary; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; C013803:alpha 2u globulin; C025500:alpha(2)-microglobulin