Single cell imaging reveals abnormal intracellular calcium signals within rheumatoid synovial neutrophils.

Intracellular calcium (Ca2+) signalling in synovial fluid (SF) polymorphonuclear leucocytes (PMN) from patients with rheumatoid arthritis (RA) was compared to RA and normal circulating blood PMN using single cell imaging. RA SF PMN stimulated by the peptide f-Met-Leu-Phe (FMLP) showed a striking difference in the release of Ca2+ from the intracellular store compared to RA and normal circulating blood PMN. Stimulation caused the release of a very dispersed, nonrestricted 'cloud' of Ca2+ in 60% of RA SF PMN compared to the highly localized and restricted 'cloud' observed in only 30% of normal circulating PMN. In the presence of extracellular Ca2+, both RA SF and normal blood PMN showed heterogeneity in both the timing and magnitude of their cytosolic free Ca2+ signalling. These observations imply that the Ca2+ signalling mechanism in RA SF and RA blood PMN has been primed in a way which could exacerbate the release of inflammatory mediators. This may have serious implications for explaining the aberrant behaviour of SF PMN in RA.