ALTERATIONS IN CA2-TRANSDUCTION IN CRITICALLY ILL SURGICAL PATIENTS( SIGNAL)

related disorders such as systemic inflammatory response syndrome (SIR S) continue to be a setting may in part be mediated at the level of ea rly signal transduction in monocytes and neutrophils as manifested by changes in intracellular free Ca2+. Methods. Monocytes and neutrophils were isolated from patients in the intensive care unit who met the cr iteria for SIPS and from normal volunteers. Cells were loaded with the Ca2+-sensitive fluorescent dye Indo-1 and stimulated with the chemota ctic peptide S-Met-Leu-Phe (fMLP). Changes in intracellular calcium io n concentration were measured by flow cytometry. Results. Patient mono cytes exhibited a decreased Ca2+ flux (43% +/- 3.1%) as compared with normal monocytes (63% +/- 2.5%) (p < 0.05). Patient neutrophils also e xhibited a decreased Ca2+ flux in response to fMLP of 58% +/- 3.7% ver sus 69.3% +/- 3.1% Sor normal neutrophils (p < 0.05). Incubation of pa tient cells in normal plasma reversed this dysfunction and showed an i mproved Ca2+ flux to 60% +/- 2.7% for monocytes and 71% +/- 3.7% Sor n eutrophils (p < 0.05). Conversely, calcium flux was decreased in both normal monocytes (42.3% +/- 3.1%) and normal neutrophils (55.4% +/- 3. 8%) after incubation in SIPS patient plasma (p < 0.05). Incubation of normal fMLP. Conclusions. Patients with SIRS exhibit alterations in ea rly signal transduction after stimulation with fMLP in monocytes and n eutrophils. This effect appears to be mediated by a soluble factor bec ause the defect in SIRS patient cells can be reversed by incubation in normal plasma and normal cells appear to acquire this defect after in cubation in patient plasma. Further studies are underway to identify t he factor or factors responsible Sor this functional defect.