Simona Casarini | PubMed Health

PubMed2005

Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways.

BACKGROUND: CXCL8/IL-8 is the most significant chemokine for neutrophils, and CXC chemokine receptor (CXCR) 1 and 2 are its 2 receptors, which are downmodulated by CXCL8/IL-8 and endotoxin on activated neutrophils. OBJECTIVE: We sought to evaluate the expression of the CXCL8/IL-8 receptors and the activation marker CD11b on neutrophils in peripheral blood and in the site of airway inflammation. METHODS: The flow cytometric expression of CXCR1, CXCR2, and CD11b was evaluated on peripheral blood and induced sputum neutrophils in patients with nonsevere asthma with greater than 60% sputum neutrophils, in patients with chronic obstructive pulmonary disease (COPD), and in healthy control subjects. RESULTS: Asthmatic patients and patients with COPD had comparable expressions of CXCR1, CXCR2, and CD11b on peripheral blood and sputum neutrophils. Compared with control subjects, the peripheral neutrophil expression of CXCR2 was lower in patients with COPD ( P = .03) and that of CD11b was higher in asthmatic patients and patients with COPD ( P < .02 and P < .002). The expression of the CXCL8/IL-8 receptors on sputum neutrophils was markedly lower than on peripheral blood neutrophils ( P < .0001). The downmodulation of CXCL8/IL-8 receptors was also present in healthy control subjects but less than that seen in asthmatic patients. The difference between peripheral blood and sputum expression of CXCL8/IL-8 receptors correlated with serum CXCL8/IL-8 levels. In asthmatic patients the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with sputum neutrophils. CONCLUSION: In neutrophilic asthma the expression of CXCL8/IL-8 receptors on peripheral and sputum neutrophils is similar to COPD and negatively correlated with the inflammatory infiltrate in the airways. The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors.

Adolescent↗

PubMed2002

Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment.

Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with lambda isotype and lambdaVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal V(lambda) regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the lambdaIII family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the lambdaIII and lambdaVI families, namely 3r (22% of cases, lambdaIII) and 6a (20%, lambdaVI), contributed equally to encode 42% of amyloid V(lambda) regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%, P =.024; 6a, 2.3%, P =.0008, chi2 test); (5) the J(lambda)2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P =.03), and this might be related to preferential J(lambda)2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that V(lambda)-J(lambda) expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments, 3r and 6a, can thus account for the lambda light-chain overrepresentation typical of this disorder.

Adult↗