Differential expression and regulation of the non-integrin 37/67-kDa laminin receptor on peripheral blood leukocytes of healthy individuals and patients with rheumatoid arthritis.

The non-integrin 37/67-kDa laminin receptor (LAMR1) is a complex protein with diverse functions. LAMR1 is widely expressed in epithelial cells and recently it was reported on neutrophils and a subset of activated T cells. Ligation of LAMR1 on peripheral blood mononuclear cells (PBMC) downregulated LPS-induced TNFα production, suggesting immune functions. However, its expression on primary monocytes remain unknown. Interestingly, LAMR1 mRNA is downregulated in PBMC of patients with early rheumatoid arthritis (RA), and low gene expression is an independent predictor of poor response to anti-TNFα treatment, suggesting a role in RA pathogenesis. We found LAMR1 was constitutively expressed on all peripheral blood monocytes and a subset of B cells from healthy individuals and patients with RA and it was abundantly present in synovial tissue of patients with RA. On monocytes and synovial tissue lower levels of LAMR1 expression tended to correlate with increased disease activity scores. In vitro treatment of monocytes with IFNγ or IL-10 up-regulated surface LAMR1 in healthy individuals and patients with RA with greater effects observed in healthy individuals. Importantly, treatment with IFNγ significantly increased specific binding of monocytes to laminin-1. TNFα and IL-1ß caused marginal downregulation of LAMR1 in patients but effects in controls were variable. Taken together, constitutively expressed LAMR1 on monocytes is differentially regulated by pro-inflammatory and immune-regulatory cytokines suggesting LAMR1 may regulate the threshold and amplitude of their activation and migration. Decreased levels in patients with RA may indicate loss of this potentially critical homeostatic regulation thereby contributing to the excessive inflammation.

Major laminin-binding and F-actin-linked glycoproteins of neutrophils.

Two major EHS-laminin-binding membrane glycoproteins--with apparent molecular masses of 50 kD and 18 kD--were shown by protein blotting in membrane fractions of porcine neutrophils. These galectin-like glycoproteins (binding probably via the N-acetyllactosamine sequences to laminin) could also be detected by labelled F-actin in protein blots. Following 35 min adhesion to the plastic surface, the relative amount of the 18 kD protein increased considerably in the light (plasma membrane) and in the dense (intracellular) membrane fractions of the attached cells; the 50 kD polypeptide (identified as a CD14-like protein) seemed to accumulate characteristically in the dense membrane fraction. These observations imply that direct connections could be formed between membrane glycoproteins and microfilaments during cell-substrate adhesion which may be preceded by enhanced cell surface targeting of certain adhesion receptors.