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Multiple cholesterol stones are associated with more biliary complications and show more rapid cholesterol nucleation than solitary stones. Group II phospholipase A2 (PLA2-II) may play a critical role in the process of mucosal inflammation, which in turn may produce pronucleating agents. PLA2-II concentrations in gallbladders and gallbladder bile from patients with different types of gallstone disease were assayed to correlate PLA2-II with alterations in biliary composition.PLA2-II protein concentrations were assayed immunoradiometrically using monoclonal antibodies against human splenic PLA2-II.Immunoreactive PLA2-II levels in gallbladder bile were significantly higher in patients with multiple cholesterol stones (68.2 +/- 6.3 ng/dL, mean +/- SEM; n = 24) than in those with solitary stones (24.9 +/- 2.8; n = 20; P0.01), those with multiple pigment stones (24.2 +/- 3.7; n = 18; P0.01), or control subjects (13.4 +/- 1.7; n = 19; P0.01). Increased biliary immunoreactive PLA2-II levels in multiple cholesterol stones were associated with a concomitant increase in the lysophosphatidylcholine to phosphatidylcholine ratio; free arachidonate, protein, and hexosamine concentrations; and gallbladder bile viscosity. The gallbladders showed an increased PLA2-II protein mass and steady-state messenger RNA levels, which was associated with increased prostaglandin E2 levels.Increased biliary PLA2-II may be of pathogenetic importance in multiple cholesterol stones, probably through potentiating gallbladder mucosal inflammation with associated biliary alterations favoring cholesterol crystal formation.

mphoid cells increased in the medulla during 24 to 48 h. The number of cax~cer cells in the marginal sinus reached the maximmu at 6 h, then declined until 48 h, but significant proliferation was observed front 4 days atier inoculation. The marginal sinus was then filled with cancer cells and expanded. At this period, the ED3 macrophages accumulated and intermingled with cancer ceils, Some cancer ceils resulted in apoptosis, being incorporated by the ED3 macrophages. In LN depleted of macrophages with liposomes containing DMDP, cancer cells massivdy invade the LN parenchyma TNF-e~ and IL-I[3 in the LN significanfly increased at ] and 3 h, respectively [1-2 increased significantly during 6 to 24 h. These cytokines returned to the basal level thereaher. 1FN-y or IL-12 did not increase at earlier periods, but significantly decreased from 24 to 96 h Localization of IL113 positive cells was consistent with that of ED2 macrophage in the medulla, but not of ED3 macrophage. TNF-cx positive cells were found in the germinal centen Conclusions: Immune responses in thks study include germinal center activation, followed by lymphoid cell pmlileration in the medulla and sinus histiocytosis, which mimic histological maniIestations of regional LN in cancer patients with improved survival Thus, LN did have capability to eliminate carmer cells temporarily. Depiction of immunocompetent cells due to deterioranon of cytokine induction may be responsible for later loss of the capabihty to prevent metastasis Macmphages contribute as a first line defense against cancer invasion. There is a different role in preventing metastasis between marginal atrd medullary sinus macrophages.