Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression.

Although the immune system, inflammation, and cellular metabolism are linked to diseases associated with dyslipidemias, the mechanism(s) remain unclear. To determine whether there is a mechanistic link between lipid availability and inflammation/immune activation, we evaluated macrophage cell lines incubated under conditions of altered exogenous and endogenous lipid availability. Limiting exogenous lipids results in decreased lysosomal acidity and decreased lysosomal enzymatic activity. Both lysosomal parameters are restored with the addition of oleoyl-CoA, suggesting that fatty acids play a role in the regulation of lysosomal function. Cell surface expression of major histocompatibility complex (MHC)-encoded molecules is also decreased in the absence of exogenous lipids. Additionally, we observe decreased gamma-interferon stimulation of cell surface MHC class II. Using cerulenin to limit the endogenous synthesis of fatty acids results in decreased cell surface expression of MHC class II but does not appear to alter lysosomal acidity, suggesting that lysosomal acidity is dependent on exogenous, but not endogenous, fatty acid availability. Testing these conclusions in an in vivo mouse model, we observed statistically significant, diet-dependent differences in lysosomal acidity and MHC class II cell surface expression. Collectively, these data demonstrate a mechanistic link between lipid availability and early events in the immune response.

Unusual presentation of anaerobic osteomyelitis.

Acute hematogenous osteomyelitis was detected in a 23-year-old sickle-cell patient after standard radiographs of the right femur showed gas within the medullary cavity. Three anaerobic organisms were cultured from surgically aspirated materials, but no source of infection was found. After surgical drainage and six weeks of intravenous clindamycin therapy, there was clinical improvement and radiographic resolution of the gas formation.

The V region sequence of lambda Bence-Jones protein Wh: evidence for separate germ-line sets within lambda-subgroups.

The complete variable region sequence of the glycosylated Bence-Jones protein Wh has revealed that the most hypervariable segments of the first and third complementarity-determing regions (CDR) are identical with those of another glycosylated Bence-Jones protein (Nei) of the same lambda-subgroup. The carbohydrate is attached in both proteins at the identical sequences in the third CDR, and the sequences of the first CDR differ at only one position in fourteen. Because CDR sequence comparisons more sensitively reflect overall germ-line V gene similarities, proteins Wh and Nei could possibly reflect a "set" relationship analogous to the mouse V kappa isotype. Cluster analyses of currently available V lambda sequences supported this suggested relationship.