ABS A0 ). 1. The clotting mechanism of Balanus nubilt was found to be affected by calcium ion with a threshold value for induced clot formation of blood i diluted 1:3:l w h 10% EDTA and 3% Naol respectively falling between 0.025M and O.1M calcium chloride. 2. The clotting mechanism of B. nubilus was also found to be affected by hydrogen ion concen¬ tration with an optimum value for clot formation at a ph value of approximately 6.7. TNA INTRODUCTION The blood clot formed in decapod crustaceans was described by Fredericg (1879) and Halliburton (1665) as a jelly-like aglutination, consisting of a cross-hatching of fibers to which is attached an amorphous, granulated gel. Although avind (1948) obse ved an effect induced by variations in hydrogen ion conent ation and alium io on the clot ng mech¬ anism in some decapod crustaceans, no investigation of the effect of hydrogen ion and calcium ion on the process in cirripeds has been reported. This is a report of a study of the clotting mechanism of Balanus nubilus (Darwin, 1854) and the effect of calcium ion and hydrogen ion on the process. MATERIALS AND THODS Specimens of B. nubilus were collected with their basal calcareous plates intact from the pliings of Fisherman's Wharf, Monterey, California, and kept 29 in running sea water until used. The blood was removed by puncturing the basal plate, removing excess debris w ith forceps, and mantle cavity fluid with a water aspirator. Blood was withdra n from the ventral thoracic sinus using aone ml. plas i syringe contain ing 0.4 ml. of a 10 solution of Ethylenediaminetetraacetic acid disodium salt (EDTA) adjusted to a pH of 7.1 and fitted with a 22-gauge needle coated with Beckman's sicote, to minimize contact with wettable su faces. Generally, 0.6 ml. samples of blood were withdrawn rred to a glass centrifuge tube conta: ining and transfe: 10% EDTA and 3% Nacl so that the final ratio of blood, EDTA, and Nacl was 1:3:l respectively. iis sample was then centrifuged immediately at approximately 1500xG to remove any particulate matter, including any clot formed during the collect tion of blood. One ml. aliquots of the supernatant were used in the eper ntal procedures described below and amounted to a l:5 dilution of the blood. Acetate and tris (hydroxymethyl) a inomethane (Tris) buffers were prepared acco ing to the method of Gomori (1955); except buffers with a pH from 2.0 rom a mixture of 50 ml. of 0.2M to 3.5 were preparedi acetic acid (diluted to a total volume of 100 ml.) and 5 ml. of 0.2M sodium acetate to which was added glacial acetic acid until the mixture reached the desired pH values. Similarly, buffers in the range from 6.7 to 10.0 were prepared from 50 ml. of a 0.2M Tris solution (diluted to a total volume of 200 ml.) to which was added Tris u til the desired pH values were reached. 56 The amount of clot was estimated in terms of its protein content as measured by the method of Lowry (1951) after dissolving the clot in 2% Naco, in O.1N NaoH. RESULT he ef? slect of calcium ion on clot formation To a one ml. sample of diluted blood containing 2TA was added an additional ml. of 3% Nagl, plus one ml. of a solution of calcium chloride of molarities ranging from 0.00625M to O.5M. Samples were allowed to stand at room temperature for 6 hours, then centrifuged. the supernatant removed, and the clot washed twice in a 3% Nacl solution.. The clot was then dissolved in 5 ml. of a 2% Naco, in O.lN NaoH solution and one mi. aliquots were removed for protein analysis. Fig. 1. presents the results. Even without the addition of calcium chloride, a small amount of par- ticulate protein was formed. This small amount remained constant until the solution of calcium chloride added exceeded 0.025M. The addition of levels in excess of this amount induced clot formation. The fect of hydrogen ion concentration on clot 0 ion To a one ml. sample of diluted blood containing EDTA was added one ml. of buffer and one ml. of 0.2M calcium chloride solution, an amount sufficient to yield near maximum clot. The procedure follows exactly the protocol used for calcium dependency above. Fig. 2. relates pH values to the effectiveness of a 0.2M calcium chloride solution to induce clot formation. Between pH 2.0 and 4.5 the amount of O particulate protein remains at a low level approx- lately equal to the amount of protein obtained with the pre-threshold concentrations of calcium in Fig. 1. At pil values above 4.5 the amount of clot increases steadily to a maximum value at a pH equal to 6.7. hen decreases at approximately the same rate, reaching a zero clot value at a pH of 10.0. relationship of clot protein to Sreod Changes in the soluble protein content of the blood were analyged as indicated in Fig. 3. An anal- ysis of the first separation (Supe rnatant I and Sediment 1) indicates a total protein content of approxi mately 35 ng. protein/ ml. of which 19% to 27% was in the form of clot protein formed during the collection of blood. lus any proteinaceous substances and any cellular mponents attached to the clot. Although repeated microscopic examinations of the blood failed to reveal discreet cellular elements, any cellular blood com¬ ponents present in low concentrations would be contained thin Sediment I. A further breakdown of Sedi ent I shows that 65% is in the form of an insoluble protein. while the remaining proteins could be washed away by either 103 EDTA or 3% Nacl. The clot formed in Sedi- ment I could not be reversed by treatment with EDTA. No di erences in the solvent property of Nagl and WDTA was observed. This treatment with TA correlates with parallel experi. ments done on the reversibilit of washed Sediment II. In as ilar treatment y 3 ml. of 3% Nacl and 3 ml. of 10% EDTA on a clot in¬ duced by 0.2M calcium chloride, the values were found to be equal. Treatment with 6 ml. and 9 ml. of 10% 32 0 D failed to lessen the protein content si nificantly. n analysis o Super natant I shows that 29% of the proteins in this solution are capable of ming clot. and that there is a negl: jible amount of proteinaceous substances attached to the clot at this point (Sediment — nally,t tio of the 1). votal clo protein th to oolten ren OT. een 32% and 35%. D SION The effect of e eleium sug os involvement of this ion in the clotting mechanism, but the di terms i oft involvement w vill require fu ther investigation. The possible displacemen it by calcium of some othe: dio: r trivalent ion from a chelated complex canno¬ be ruled ou The effect of hy drogen ion concentration canno e eo ned as the effet of phont he chelat ablll of 4. Mal riel and Calvin (1952) point out th the chelating power of EDTA is zero between a phof 1.0 and 4.8, acceler maximum at a ating to a of 7.8, and then remaining at this level. his relationship between pH and chelat power does not explain the high amounts of clottis induced by calciu between a ph of 7.0 and 8.5 where chelation is at a um; nor the pH optimum of 6.7 for clott which is almost at the m mum for chelating power; nor the reasing amounts of clot fo ation beween a ph of 5.0 and 6.7 which corresponds to a range of aidly increusing chelating ability; nor the low amounts of lot ig observed between a pH of 2.0 and 4.5 where 27- chelatir agower is esse tially zero. The efore, it 38 O appoars, that there are pi-dependent factors inherent in the clotting mechanism. Mlood clotting in cirripeds, as studied in 2. nubilus, shows similarities to the process as studied in other crustaceans, especially in decapods (Glavind, 1948). ACKNOWLED GEMENT Dhil7 I am grateful to Dr. John Filllips, whose advice and assistance made this study possible. . O O C + S t 9 S . 12-282 8 C O 2 O 0 8 O 8 0 O 59. 12-282 20 Squares to the Inch Ste I O1 The s falum ion lotted rouce 6 hour rotein ure preser the blood and ED TA i uion of Balanus bloo 7 - igure2 he effet. ion of ogen amount of clotted podu ed: ot nthe sence of added calci e aliquot of the blood a mitu 5 dilution of lood. ++- f clot anvere lationshi o total blood protein. unt aliqu Wach sal a 6 h a orot C R ERENCES Darwin, C.H. 1854 A Monograph on the sub-class Cirripe Verrucidae,etc). Ray lia (Balanidae Society, London, p. 307. Fredericg, L. (187 Note sur le sang de l'Homar Sull. acad. roy. Bel ique (ser. 2) 47: 409-413. Glavind, J. (1948) Studies on the coagulation of tacean blood. 137pp. Nyt Nordisk Forlag, Cry Arnold Busck, Copenhagen. Gomori, G. (1955) Preparations of buffers used in f Enzymology, enzyme studies, cited in Methods Vol. 1 ed. by Colowick, S. and Kaplan, .. Academic Press, Inc. New York, pp. 138-146. Halliburton, W.D. (1885) On the blood of decapod Crustacea. J. ysiol., 6: 300-335. Lowry, Rosebrough, Farr, and Randall (1951) Protein measurement with the Folin Phenol Reagent. J. Biochem. 193: 265-275. Martell, A. and Calvin, M. (1952) Chemis of the Metal Chelate Compound pp. 494-495. Prentice- Hall, Inc, New lork.