Differential expression of cysteine-rich intestinal protein in liver and intestine in CCl4-induced inflammation.

Cysteine-rich intestinal protein (CRIP) is a double zinc finger (LIM domain) protein that is developmentally regulated but has an unknown function. CRIP is highly expressed in the intestine, but expression is low in liver. To determine if CRIP expression is regulated under altered physiological status, we used CCl4-induced injury as a model to produce hepatic injury and systemic effects associated with inflammation. Since CRIP is a zinc finger protein and zinc decreases the hepatic response to CCl4, the effect of supplemental dietary zinc (300 mg/kg diet) was also examined. Our results show that this supplemental level of dietary zinc did not affect the index of hepatic injury (plasma alanine aminotransferase), indicating zinc did not have a protective effect. Liver CRIP mRNA increased with CCl4 and CRIP protein was shown by immunohistochemistry to be localized in hepatocytes near the vascular supply. In the intestine, CCl4 caused a transient decrease in CRIP mRNA, but supplemental dietary zinc treatment prevented this decrease. These current results show that CRIP expression changes in response to cellular damage due to acute hepatic injury and are consistent with a functional role for CRIP in proliferation, differentiation, or turnover.

Lipopolysaccharide regulates cysteine-rich intestinal protein, a zinc-finger protein, in immune cells and plasma.

Cysteine-rich intestinal protein (CRIP), a double zinc-finger LIM protein, is expressed in great abundance in the intestine. We have found comparable levels of CRIP mRNA in peritoneal macrophages, peripheral blood mononuclear cells (PBMC), and lesser amounts in thymus and spleen. Because CRIP expression was high in immune cells, rats were challenged with lipopolysaccharide (LPS) to determine whether expression was altered during the acute-phase immune response. Immunocytochemistry showed that, in adherent mononuclear cells, CRIP protein was localized in the cytoplasm. CRIP mRNA levels increased over time after LPS injection in peritoneal macrophages, PBMC, spleen, and intestine. No changes in CRIP mRNA level were seen in either liver or thymus. In PBMC, the level of CRIP mRNA decreased before increasing later in the acute-phase immune response. CRIP protein was found in the plasma. Shortly after LPS administration plasma CRIP decreased, suggesting that CRIP was either passively diffused out of capillaries or was actively shunted into tissues to execute its function. Increased CRIP expression seen in response to LPS suggests that CRIP may play a role in immune cell activation or differentiation or in processes associated with cellular repair.

Serotransferrin, ovotransferrin and metallothionein levels during an immune response in chickens.

Extracellular iron-binding proteins function in iron transport, iron scavenging and bactericidal activity. To determine whether the levels of chicken iron-binding proteins are altered during an immune challenge, young broiler chicks and 40-week-old hens were injected with lipopolysaccharide (LPS). Serum transferrin and liver mRNA for serum transferrin increased at 24 hr after injection. Increased levels of serum transferrin and hepatic mRNA for serum transferrin define chicken serum transferrin as an acute-phase protein. Magnum mRNA for ovotransferrin decreased 24 hr after the immune challenge in hens. Hens had also stopped ovulating, suggesting that synthesis of all egg proteins was decreased.

Maternal-iron-deficiency effects on peritoneal macrophage and peritoneal natural-killer-cell cytotoxicity in rat pups.

Cytotoxicity of peritoneal macrophages (pMs) and peritoneal natural killer (pNK) cells toward xenogenic tumor cells was studied in anemic, suckling rats. Dams were fed 6, 12, or 250 mg Fe/kg diet ad libitum throughout gestation and lactation. Pups were injected intraperitoneally with 10(5) plaque-forming units of virus. Four days later cytotoxicity of pMs and pNK cells against YAC-1 mouse lymphoma cells was measured. Body weight, hemoglobin, hematocrit, and viable cell yield of pups were significantly decreased with decreasing dietary iron. pM cytotoxicity was significantly impaired in anemic pups at pM-target-cell ratios of 10:1 and 30:1 at 4 and 16 h (P less than or equal to 0.03). pNK-cell cytotoxicity was significantly impaired in anemic pups at pNK-target-cell ratios of 10:1 and 50:1 at 16 h. Iron-deficient diet consumed by dams throughout gestation and lactation resulted in anemic offspring whose immunologic defense by pMs and pNK cells against xenogenic tumor cells was significantly reduced.