Increased CD11/CD18 expression on peripheral blood leucocytes of patients with sarcoidosis

Abstract

SUMMARYSarcoidosis is a tnultisystem disease of unknown etiology characterized by non-caseating granulomata, formed mainly from macrophages surrounded by lymphocytes and plasma cells. Using a novel method for the preparation of blood leucocytes for flow cytometry, we report increased expression of LeuCAMs (CD 11/CD 18) on peripheral blood leucocytes of 11 Caucasian and 10 Afro-Caribbean patients with sarcoidosis compared with age-, sex-and race-matched controls. Whilst the percentages ofthe cells expressing CDl 1/CD 18 were no different, the density, expressed as mean fluorescence intensity (MFI), was greater for all leucocytes in sarcoids than in normal individuals. The expression of intercellular adhesion molecule-1 (ICAM-1), a ligand for LFA-1 which is expressed on all leucocytes, was not significantly different from normal, whereas HLA-DR was expressed more intensely on sarcoid monocytes (/" < 001) and blood lymphocytes (P < 0 005) than control cells. Our findings are consistent with leucocyte activation although we were unable to confirm reports of elevated tumour necrosis factor-alpha (TNF-a) in the patients' plasma using an ELISA. Increased expression of adhesion molecules on peripheral blood leucocytes may play a role in the cellular extravasation, aggregation, and granuloma formation seen in sarcoidosis.

Circulating adhesion molecules in sarcoidosis

“…Eleven were AfroCaribbean, mean age 36 years (range 21-63 years) and 12 were Caucasian, mean age 36 years (range 27-54 years). Nineteen of the patients were included in a previous study [4]. Patients were not receiving corticosteroids or other immunosuppressive therapy at the time of investigations or within the previous 12 months.…”

“…Clinical information obtained from the patients included smoking habits, chest x-ray findings, graded according to conventional criteria (Stage I, hilar adenopathy without parenchymal infiltrates; Stage II, hilar adenopathy with parenchymal infiltrates; and Stage III, fibrosis or infiltrates without hilar adenopathy), symptom duration and organ involvement, SACE levels and erythrocyte sedimentation rate (ESR) as well as lung function tests. This information was obtained for tests done within 1 week of the blood being taken for the study reported here and elsewhere [4]. Clinical information on 19 of these patients has previously been reported [4].…”

“…This information was obtained for tests done within 1 week of the blood being taken for the study reported here and elsewhere [4]. Clinical information on 19 of these patients has previously been reported [4]. Of the remaining four patients, three were Afro-Caribbean and one was Caucasian, all were chest x-ray stage II, and one had sarcoid uveitis as well as thoracic disease.…”

“…The presence of granulomata and immunopathology at local sites is accompanied by systemic abnormalities, including changes in the proportions of circulating lymphocyte subpopulations and their activation [3,4], activation of circulating monocytes [4], alterations in circulating enzyme levels, particularly serum angiotensin converting enzyme (SACE) [5], and alterations in calcium levels [6]. We have recently added to these by showing that circulating lymphocytes, polymorphs and monocytes express elevated levels of the leucocyte integrins CDl 1/CD 18 [4]. Increased cell surface expression of CD11/CD18 may favour intercellular adhesion, which is important in the development of cellular immune responses or the extravasation of cells from the circulation.…”

“…The objective of this study was to measure the levels of circulating VCAM-1, ICAM-1 and E-selectin in serum samples obtained from a group of sarcoidosis patients previously shown to have an increase in their mean level of expression of CDl 1/ CD 18 on their peripheral blood leucocytes [4]. Correlations were sought between circulating and cell surface adhesion molecule levels and various parameters of disease activity.…”